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https://www.readbyqxmd.com/read/29223100/activation-of-anti-oxidant-nrf2-signaling-by-enone-analogues-of-curcumin
#1
Lorraine M Deck, Lucy A Hunsaker, Thomas A Vander Jagt, Lisa J Whalen, Robert E Royer, David L Vander Jagt
Inflammation and oxidative stress are common in many chronic diseases. Targeting signaling pathways that contribute to these conditions may have therapeutic potential. The transcription factor Nrf2 is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. Nrf2 is widespread in the CNS and is recognized as an important regulator of brain inflammation. The natural product curcumin exhibits numerous biological activities including ability to induce the expression of Nrf2-dependent phase II and anti-oxidant enzymes...
November 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29222947/safety-and-efficacy-of-guselkumab-in-japanese-patients-with-moderate-to-severe-plaque-psoriasis-a-randomised-placebo-controlled-ascending-dose-study
#2
O Nemoto, K Hirose, S Shibata, K Li, H Kubo
BACKGROUND: The Interlukin-23 (IL-23)/Interlukin-17 (IL-17) pathway is central in the pathogenesis of psoriasis. The favourable efficacy and safety of guselkumab, an IL-23 specific monoclonal antibody, has been demonstrated in global Phase 3 studies of plaque psoriasis. OBJECTIVES: To evaluate the safety, efficacy and pharmacokinetics of a single-dose subcutaneous guselkumab in Japanese patients with moderate-to-severe plaque psoriasis. METHODS: Patients with ≥ 10% of total body surface area (BSA) involvement and a Psoriasis Area and Severity Index (PASI) ≥12 were randomised (5:1) to receive guselkumab or placebo in 4 cohorts of this double-blind, placebo-controlled, single ascending dose, single-centre study...
December 9, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/29222911/current-and-future-therapeutic-regimens-for-non-alcoholic-fatty-liver-disease-nafld-and-non-alcoholic-steatohepatitis-nash
#3
REVIEW
Zobair M Younossi, Rohit Loomba, Mary E Rinella, Elisabetta Bugianesi, Giulio Marchesini, Brent A Neuschwander-Tetri, Lawrence Serfaty, Francesco Negro, Stephen H Caldwell, Vlad Ratziu, Kathleen E Corey, Scott L Friedman, Manal F Abdelmalek, Stephen A Harrison, Arun J Sanyal, Joel E Lavine, Philippe Mathurin, Michael R Charlton, Naga P Chalasani, Quentin M Anstee, Kris V Kowdley, Jacob George, Zachary D Goodman, Keith Lindor
NASH/NAFLD is rapidly becoming one of top causes of cirrhosis, hepatocellular carcinoma and indication for liver transplantation. Except for life style modification through diet and exercise, there are currently no other approved treatments for NASH/NAFLD. Although weight loss can be effective, it is hard to achieve and sustain. In contrast, bariatric surgery can improve metabolic conditions associated with NAFLD and has been shown to improve liver histology. In order to have approved regimens for treatment of NASH/NAFLD, a number of issues that must be addressed...
December 9, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29222693/neuroblastoma-pathogenesis-deregulation-of-embryonic-neural-crest-development
#4
REVIEW
Julie A Tomolonis, Saurabh Agarwal, Jason M Shohet
Neuroblastoma (NB) is an aggressive pediatric cancer that originates from neural crest tissues of the sympathetic nervous system. NB is highly heterogeneous both from a clinical and a molecular perspective. Clinically, this cancer represents a wide range of phenotypes ranging from spontaneous regression of 4S disease to unremitting treatment-refractory progression and death of high-risk metastatic disease. At a cellular level, the heterogeneous behavior of NB likely arises from an arrest and deregulation of normal neural crest development...
December 8, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29222471/spatial-competition-constrains-resistance-to-targeted-cancer-therapy
#5
Katarina Bacevic, Robert Noble, Ahmed Soffar, Orchid Wael Ammar, Benjamin Boszonyik, Susana Prieto, Charles Vincent, Michael E Hochberg, Liliana Krasinska, Daniel Fisher
Adaptive therapy (AT) aims to control tumour burden by maintaining therapy-sensitive cells to exploit their competition with resistant cells. This relies on the assumption that resistant cells have impaired cellular fitness. Here, using a model of resistance to a pharmacological cyclin-dependent kinase inhibitor (CDKi), we show that this assumption is valid when competition between cells is spatially structured. We generate CDKi-resistant cancer cells and find that they have reduced proliferative fitness and stably rewired cell cycle control pathways...
December 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/29222314/plasma-exchange-in-thrombotic-microangiopathies-tmas-other-than-thrombotic-thrombocytopenic-purpura-ttp
#6
REVIEW
Jeffrey L Winters
Thrombotic microangiopathies (TMAs) are a diverse group of disorders that are characterized by common clinical and laboratory features. The most commonly thought-of TMA is thrombotic thrombocytopenic purpura (TTP). Because of the marked improvement in patient mortality associated with the use of therapeutic plasma exchange (TPE) in TTP, this therapy has been applied to all of the TMAs. The issue, however, is that the pathophysiology varies and in many instances may represent a disorder of the endothelium and not the blood; in some cases, the pathophysiology is unknown...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222305/biology-of-cns-lymphoma-and-the-potential-of-novel-agents
#7
REVIEW
James L Rubenstein
Primary and secondary CNS lymphomas are aggressive brain tumors that pose an immense challenge to define in terms of molecular pathogenesis, as well as to effectively treat. During the past 10 years improvements in survival have been achieved with the implementation of anti-CD20 immunotherapy and optimization of dose-intensive consolidation strategies. The applications of whole-exome sequencing, comparative genomic hybridization, transcriptional profiling, and examination of the tumor microenvironment, particularly in the context of clinical investigation, provide insights that create a roadmap for the development and implementation of novel targeted agents for this disease...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222294/incorporating-novel-approaches-in-the-management-of-mds-beyond-conventional-hypomethylating-agents
#8
REVIEW
Olatoyosi Odenike
In the last decade, the treatment of higher-risk myelodysplastic syndromes (MDS) has revolved around the azanucleosides, azacitidine and decitabine, which at lower doses are postulated to work predominantly via their effects on inhibition of DNA methyltransferases and consequent DNA hypomethylation. For patients who relapse after, or do not respond to, hypomethylating agent therapy, the outcome is dismal, and new agents and approaches that have the potential to alter the natural history of these diseases are desperately needed...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222281/improved-biological-insight-and-influence-on-management-in-indolent-lymphoma-talk-3-update-on-nodal-and-splenic-marginal-zone-lymphoma
#9
REVIEW
Catherine Thieblemont
Splenic marginal zone lymphoma (SMZL) and nodal marginal zone lymphoma (NMZL) are rare indolent chronic B-cell lymphomas. Prognosis is typically good with median survival around 10-15 years. Management is generally based on the presence of symptoms or high tumor burden. There are no standard treatments for these 2 entities, and therapeutic strategies are rapidly evolving. Clinical developments for these 2 entities are oriented by genomic studies, with largely overlapping mutational profiles involving the NOTCH, B-cell receptor (BcR) and nuclear factor κB (NF-κB) signaling, chromatin remodeling, and the cytoskeleton...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222259/controversies-in-venous-thromboembolism-to-treat-or-not-to-treat-superficial-vein-thrombosis
#10
REVIEW
Jan Beyer-Westendorf
The management of superficial vein thrombosis (SVT) is poorly defined and remains controversial overall. SVT has long been considered a benign, self-limited disease, but recent studies show that SVT carries a nonnegligible risk for recurrence, deep vein thrombosis, or pulmonary embolism. Current guidelines recommend the use of low-molecular-weight heparin or fondaparinux, but results of several surveys indicate that the majority of patients with SVT receive nonanticoagulant therapy only, which includes compression stockings or bandages, nonsteroidal anti-inflammatory drugs, topical application of heparin gel, or surgical interventions...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222253/new-monogenic-disorders-identify-more-pathways-to-neutropenia-from-the-clinic-to-next-generation-sequencing
#11
REVIEW
Seth J Corey, Usua Oyarbide
Neutrophils are the most common type of leukocyte in human circulating blood and constitute one of the chief mediators for innate immunity. Defined as a reduction from a normal distribution of values, neutropenia results from a number of congenital and acquired conditions. Neutropenia may be insignificant, temporary, or associated with a chronic condition with or without a vulnerability to life-threatening infections. As an inherited bone marrow failure syndrome, neutropenia may be associated with transformation to myeloid malignancy...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222234/progress-in-adult-all-incorporation-of-new-agents-to-frontline-treatment
#12
REVIEW
Jessica Leonard, Wendy Stock
Treatment of acute lymphoblastic leukemia (ALL) in adults remains a challenge, as the delivery of intensive chemotherapeutic regimens in this population is less feasible than it is in the pediatric population. This has led to higher rates of treatment-related toxicity as well as lower overall survival in the adult population. Over the past several years, a host of novel therapies (eg, immunotherapy and targeted therapies) with better tolerability than traditional chemotherapy are now being introduced into the relapsed/refractory population with very encouraging results...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222171/tankyrase-inhibition-enhances-the-anti-proliferative-effect-of-pi3k-and-egfr-inhibition-mutually-affecting-%C3%AE-catenin-and-akt-signaling-in-colorectal-cancer
#13
Nina T Solberg, Jo Waaler, Kaja Lund, Line Mygland, Petter A Olsen, Stefan Krauss
Over-activation of the WNT/β-catenin signaling axis is a common denominator in colorectal cancer (CRC). Currently there is no available WNT inhibitor in clinical practice. Although tankyrase inhibitors have been proposed as promising candidates there are many CRC models that do not respond positively to tankyrase inhibition in vitro and in vivo. Therefore, a combinatorial therapeutic approach combining a tankyrase inhibitor (G007-LK) with PI3K (BKM120) and EGFR (Erlotinib) inhibitors in CRC was investigated...
December 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29222069/cooperativity-between-different-trna-modifications-and-their-modification-pathways
#14
REVIEW
Mikołaj Sokołowski, Roland Klassen, Alexander Bruch, Raffael Schaffrath, Sebastian Glatt
Ribonucleotide modifications perform a wide variety of roles in synthesis, turnover and functionality of tRNA molecules. The presence of particular chemical moieties can refine the internal interaction network within a tRNA molecule, influence its thermodynamic stability, contribute novel chemical properties and affect its decoding behavior during mRNA translation. As the lack of specific modifications in the anticodon stem and loop causes disrupted proteome homeostasis, diminished response to stress conditions, and the onset of human diseases, the underlying modification cascades have recently gained particular scientific and clinical interest...
December 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29222042/antiangiogenic-compounds-well-established-drugs-versus-emerging-natural-molecules
#15
Andreia Ribeiro, Rui M V Abreu, Madalena M Dias, Maria Filomena Barreiro, Isabel C F R Ferreira
Angiogenesis is the natural and physiologic process of growing blood vessels from pre-existing ones. Pathological angiogenesis occurs when the precise balance of all the molecular pathways that regulate angiogenesis is disrupted, and this process is a critical step in many diseases, including cancer. A limited number of antiangiogenic synthetic drugs have been developed. However, due to toxicity and side effects issues, the search for alternative to existing drugs is ongoing. In this sense, natural molecules obtained from plants or macrofungi, have demonstrated extraordinary potential in the treatment of angiogenesis-related pathologies, specially taking into consideration its absence or very low toxicity, when compared to synthetic drugs...
December 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29222026/transcriptome-analysis-provides-insights-into-the-immune-responsive-pathways-and-genes-in-the-head-kidney-of-tiger-grouper-epinephelus-fuscoguttatus-fed-with-spatholobus-suberectus-phellodendron-amurense-or-eclipta-prostrata
#16
Yan Cai, Shifeng Wang, Weiliang Guo, Zhenyu Xie, Yu Zheng, Zhenjie Cao, Yongcan Zhou
The tiger grouper, Epinephelus fuscoguttatus, is an economically important fish in Southeast Asia but has been plagued by several diseases. Spatholobus suberectus (S), Phellodendron amurense (P), and Eclipta prostrate (E) are three commonly used Chinese medicinal herbs. Although previous pharmacological and clinical studies indicated that S, P, and E possess a variety of beneficial functions in mammals, little is known about their functions in farmed fish and the underlying molecular mechanism of their actions...
December 5, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29221947/-the-impact-of-patient-identification-on-an-integrated-program-of-palliative-care-in-basque-country
#17
Igor Larrañaga, Jesús Millas, Myriam Soto-Gordoa, Arantzazu Arrospide, Ricardo San Vicente, Marisa Irizar, Itziar Lanzeta, Javier Mar
OBJECTIVE: Evaluate the process and the economic impact of an integrated palliative care program. DESIGN: Comparative cross-sectional study. LOCATION: Integrated Healthcare Organizations of Alto Deba and Goierri Alto-Urola, Basque Country. PARTICIPANTS: Patients dead due to oncologic and non-oncologic causes in 2012 (control group) and 2015 (intervention group) liable to need palliative care according to McNamara criteria...
December 5, 2017: Atencion Primaria
https://www.readbyqxmd.com/read/29221895/report-on-eighth-who-meeting-on-development-of-influenza-vaccines-that-induce-broadly-protective-and-long-lasting-immune-responses-chicago-usa-23-24-august-2016
#18
Justin R Ortiz, Julian Hickling, Rebecca Jones, Armen Donabedian, Othmar G Engelhardt, Jacqueline M Katz, Shabir A Madhi, Kathleen M Neuzil, Guus F Rimmelzwaan, James Southern, David J Spiro, Joachim Hombach
In August 2016, the World Health Organization (WHO) convened the "Eighth meeting on development of influenza vaccines that induce broadly protective and long-lasting immune responses" to discuss the regulatory requirements and pathways for licensure of next-generation influenza vaccines, and to identify areas where WHO can promote the development of such vaccines. Participants included approximately 120 representatives of academia, the vaccine industry, research and development funders, and regulatory and public health agencies...
December 5, 2017: Vaccine
https://www.readbyqxmd.com/read/29221728/emulsified-isoflurane-induces-release-of-cytochrome-c-in-human-neuroblastoma-shsy-5y-cells-via-jnk-c-jun-n-terminal-kinases-signaling-pathway
#19
Zeyong Yang, Jingjing Lv, Xianfu Lu, Xingxing Li, Xiaohu An, Jianwei Wang, Hao Weng, Yuanhai Li
A large number of studies have demonstrated that inhalation anesthetic isoflurane induced neural cell death by apoptosis in various cell and animal models. Emulsified isoflurane (EIso) is a new type of intravenous preparation of isoflurane that attracts increasing research attention as a promising clinical agent due to its both advantages as an intravenous and inhalation anesthetics medication. However, its safety and underlying molecular mechanism of neurotoxicity largely remain unknown. Therefore, it is meaningful to investigate the safety of EIso and to further elucidate its mechanism of anesthetic neurotoxicity...
December 5, 2017: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/29221496/does-intensive-management-improve-remission-rates-in-patients-with-intermediate-rheumatoid-arthritis-the-titrate-trial-study-protocol-for-a-randomised-controlled-trial
#20
Naomi H Martin, Fowzia Ibrahim, Brian Tom, James Galloway, Allan Wailoo, Jonathan Tosh, Heidi Lempp, Louise Prothero, Sofia Georgopoulou, Jackie Sturt, David L Scott
BACKGROUND: Uncontrolled active rheumatoid arthritis can lead to increasing disability and reduced quality of life over time. 'Treating to target' has been shown to be effective in active established disease and also in early disease. However, there is a lack of nationally agreed treatment protocols for patients with established rheumatoid arthritis who have intermediate disease activity. This trial is designed to investigate whether intensive management of disease leads to a greater number of remissions at 12 months...
December 8, 2017: Trials
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