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https://www.readbyqxmd.com/read/28528528/ustekinumab-a-review-in-moderate-to-severe-crohn-s-disease
#1
Yvette N Lamb, Sean T Duggan
Ustekinumab (Stelara(®)) has been recently approved in the EU and the USA as intravenous induction and subcutaneous maintenance therapy for adult patients with moderately to severely active Crohn's disease who have failed or were intolerant to treatment with immunomodulators, corticosteroids or at least one tumour necrosis factor (TNF) antagonist. Ustekinumab, a monoclonal antibody to the shared p40 subunit of the proinflammatory interleukin (IL)-12 and IL-23 cytokines, has a unique mechanism of action distinct from that of TNF antagonists...
May 20, 2017: Drugs
https://www.readbyqxmd.com/read/28527975/the-reaumuria-trigyna-transcription-factor-rtwrky1-confers-tolerance-to-salt-stress-in-transgenic-arabidopsis
#2
Chao Du, Pingping Zhao, Huirong Zhang, Ningning Li, Linlin Zheng, Yingchun Wang
Reaumuria trigyna (R. trigyna) is an endangered small shrub endemic to the Eastern Alxa-Western Ordos area in Inner Mongolia, China. Based on R. trigyna transcriptome data, the Group I WRKY transcription factor gene RtWRKY1 was cloned from R. trigyna. The full-length RtWRKY1 gene was 2100bp, including a 1261-bp open reading frame (ORF) encoding 573 amino acids. RtWRKY1 was mainly expressed in the stem and was induced by salt, cold stress, and ABA treatment. Overexpression of RtWRKY1 in Arabidopsis significantly enhanced the chlorophyll content, root length, and fresh weight of the transgenic lines under salt stress...
May 4, 2017: Journal of Plant Physiology
https://www.readbyqxmd.com/read/28527887/mst1-deficiency-promotes-b-cell-responses-by-cd4-t-cell-derived-il-4-resulting-in-hypergammaglobulinemia
#3
Eunchong Park, Myun Soo Kim, Ju Han Song, Kyung Min Cho, Kyung-Hye Roh, Rana Lee, Tae Sung Kim
MST1 deficiency causes T and B cell lymphopenia, resulting in combined immunodeficiency. However, MST1-deficient patients also exhibit autoimmune-like symptoms such as hypergammaglobulinemia and autoantibody production. Recent studies have shown that the autoimmune responses observed in MST1-deficient patients were most likely attributable to defective regulatory T (Treg) cells instead of intrinsic signals in MST1-lacking B cells. Nevertheless, it is not determined how MST1 deficiency in T cells breaks B cell tolerance and causes systemic autoimmune-like phenotypes...
May 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28527763/aluminium-resistant-plant-growth-promoting-bacteria-induce-overexpression-of-aluminium-stress-related-genes-in-arabidopsis-thaliana-and-increase-the-ginseng-tolerance-against-aluminium-stress
#4
Mohamed El-Agamy Farh, Yeon-Ju Kim, Johan Sukweenadhi, Priyanka Singh, Deok-Chun Yang
Panax ginseng is an important cash crop in the Asian countries due to its pharmaceutical effects, however the plant is exposed to various abiotic stresses, lead to reduction of its quality. One of them is the Aluminum (Al) accumulation. Plant growth promoting bacteria which able to tolerate heavy metals has been considered as a new trend for supporting the growth of many crops in heavy metal occupied areas. In this study, twelve bacteria strains were isolated from rhizosphere of diseased Korean ginseng roots located in Gochang province, Republic of Korea and tested for their ability to grow in Al-embedded broth media...
July 2017: Microbiological Research
https://www.readbyqxmd.com/read/28527704/anti-madcam-antibody-pf-00547659-for-ulcerative-colitis-turandot-a-phase-2-randomised-double-blind-placebo-controlled-trial
#5
Séverine Vermeire, William J Sandborn, Silvio Danese, Xavier Hébuterne, Bruce A Salzberg, Maria Klopocka, Dino Tarabar, Tomas Vanasek, Miloš Greguš, Paul A Hellstern, Joo Sung Kim, Miles P Sparrow, Kenneth J Gorelick, Michelle Hinz, Alaa Ahmad, Vivek Pradhan, Mina Hassan-Zahraee, Robert Clare, Fabio Cataldi, Walter Reinisch
BACKGROUND: PF-00547659 is a fully human monoclonal antibody that binds to human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) to selectively reduce lymphocyte homing to the intestinal tract. We aimed to assess the efficacy and safety of PF-00547659 in patients with moderate to severe ulcerative colitis. METHODS: This phase 2, randomised, double-blind, placebo-controlled clinical trial recruited patients aged 18-65 years from 105 centres in 21 countries, with a history (≥3 months) of active ulcerative colitis extending more than 15 cm beyond the anal verge (with a total Mayo score ≥6 and a Mayo endoscopic subscore ≥2) who had failed or were intolerant to at least one conventional therapy...
May 17, 2017: Lancet
https://www.readbyqxmd.com/read/28527336/title-potassium-application-regulates-nitrogen-metabolism-and-osmotic-adjustment-in-cotton-gossypium-hirsutum-l-functional-leaf-under-drought-stress
#6
Rizwan Zahoor, Wenqing Zhao, Muhammad Abid, Haoran Dong, Zhiguo Zhou
To evaluate the role of potassium (K) in maintaining nitrogen metabolism and osmotic adjustment development of cotton functional leaves to sustain growth under soil drought and rewatering conditions, the plants of two cotton cultivars Siza 3 (low-K sensitive) and Simian 3 (low-K tolerant), were grown under three different K rates (K0, K1, and K2; 0, 150, and 300kgK2Oha(-1), respectively) and exposed to drought stress with 40±5% soil relative water content (SRWC). The drought stress was applied at flowering stage by withholding water for eight days followed by rewatering to a well-watered level (75±5% SRWC)...
May 4, 2017: Journal of Plant Physiology
https://www.readbyqxmd.com/read/28527125/diversity-and-probiotic-potential-of-lactic-acid-bacteria-isolated-from-horreh-a-traditional-iranian-fermented-food
#7
Alireza Vasiee, Behrooz Alizadeh Behbahani, Farideh Tabatabaei Yazdi, Seyed Ali Mortazavi, Hamid Noorbakhsh
The aim of this study was to evaluate the probiotic potential of lactic acid bacteria (LAB) strains isolated from Horreh. Some probiotic properties, e.g., resistance to acid, bile tolerance, antibacterial activity, and antibiotic susceptibility, were investigated. A total of 140 Gram-positive and catalase-negative isolates from Horreh were subjected to identification and grouping by cultural methods and the 16S rRNA sequencing. The new isolates were identified to be Lactobacillus (fermentum, plantarum, and brevis) Weissella cibaria, Enterococcus (faecium and faecalis), Leuconostoc (citreum and mesenteroides subsp...
May 19, 2017: Probiotics and Antimicrobial Proteins
https://www.readbyqxmd.com/read/28526921/glp-1-signalling-compensates-for-impaired-insulin-signalling-in-regulating-beta-cell-proliferation-in-%C3%AE-irko-mice
#8
Dan Kawamori, Jun Shirakawa, Chong Wee Liew, Jiang Hu, Tomoaki Morioka, Alokesh Duttaroy, Bryan Burkey, Rohit N Kulkarni
AIMS/HYPOTHESIS: We aimed to investigate potential interactions between insulin and glucagon-like peptide (GLP)-1 signalling pathways in the regulation of beta cell-cycle dynamics in vivo, in the context of the therapeutic potential of GLP-1 to modulate impaired beta cell function. METHODS: Beta cell-specific insulin receptor knockout (βIRKO) mice, which exhibit beta cell dysfunction and an age-dependent decrease in beta cell mass, were treated with the dipeptidyl peptidase-4 inhibitor vildagliptin...
May 20, 2017: Diabetologia
https://www.readbyqxmd.com/read/28526842/revealing-genome-scale-transcriptional-regulatory-landscape-of-ompr-highlights-its-expanded-regulatory-roles-under-osmotic-stress-in-escherichia-coli-k-12-mg1655
#9
Sang Woo Seo, Ye Gao, Donghyuk Kim, Richard Szubin, Jina Yang, Byung-Kwan Cho, Bernhard O Palsson
A transcription factor (TF), OmpR, plays a critical role in transcriptional regulation of the osmotic stress response in bacteria. Here, we reveal a genome-scale OmpR regulon in Escherichia coli K-12 MG1655. Integrative data analysis reveals that a total of 37 genes in 24 transcription units (TUs) belong to OmpR regulon. Among them, 26 genes show more than two-fold changes in expression level in an OmpR knock-out strain. Specifically, we find that: 1) OmpR regulates mostly membrane-located gene products involved in diverse fundamental biological processes, such as narU (encoding nitrate/nitrite transporter), ompX (encoding outer membrane protein X), and nuoN (encoding NADH:ubiquinone oxidoreductase); 2) by investigating co-regulation of entire sets of genes regulated by other stress-response TFs, stresses are surprisingly independently regulated among each other; and, 3) a detailed investigation of the physiological roles of the newly discovered OmpR regulon genes reveals that activation of narU represents a novel strategy to significantly improve osmotic stress tolerance of E...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526734/brigatinib-achieves-whole-body-and-intracranial-responses
#10
(no author information available yet)
Brigatinib is tolerable and has antitumor activity in crizotinib-resistant ALK-positive NSCLC.
May 19, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28526489/intravitreous-injection-of-aav2-sflt01-in-patients-with-advanced-neovascular-age-related-macular-degeneration-a-phase-1-open-label-trial
#11
Jeffrey S Heier, Saleema Kherani, Shilpa Desai, Pravin Dugel, Shalesh Kaushal, Seng H Cheng, Cheryl Delacono, Annie Purvis, Susan Richards, Annaig Le-Halpere, John Connelly, Samuel C Wadsworth, Rafael Varona, Ronald Buggage, Abraham Scaria, Peter A Campochiaro
BACKGROUND: Long-term intraocular injections of vascular endothelial growth factor (VEGF)-neutralising proteins can preserve central vision in many patients with neovascular age-related macular degeneration. We tested the safety and tolerability of a single intravitreous injection of an AAV2 vector expressing the VEGF-neutralising protein sFLT01 in patients with advanced neovascular age-related macular degeneration. METHODS: This was a phase 1, open-label, dose-escalating study done at four outpatient retina clinics in the USA...
May 16, 2017: Lancet
https://www.readbyqxmd.com/read/28526067/the-chimeric-monoclonal-antibody-mhcsz-123-against-human-von-willebrand-factor-a3-domain-inhibits-high-shear-arterial-thrombosis-in-a-rhesus-monkey-model
#12
Shundong Ji, Miao Jiang, Bin Yan, Fei Shen, Yang He, Aini Wan, Lijun Xia, Changgeng Ruan, Yiming Zhao
BACKGROUND: SZ-123, a murine monoclonal antibody that targets the human von Willebrand factor (VWF) A3 domain and blocks the binding of collagen, is a powerful antithrombotic. In a Rhesus monkey model of thrombosis, SZ-123 had no side effects, such as bleeding or thrombocytopenia. METHODS: The mouse/human chimeric version of SZ-123, MHCSZ-123, was developed and maintained inhibitory capacities in vitro and ex vivo after injection into monkeys. CHO-S cells were selected for stable expression of MHCSZ-123...
May 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28525813/ammonia-stress-on-nitrogen-metabolism-in-tolerant-aquatic-plant-myriophyllum-aquaticum
#13
Qingyang Zhou, Jingqing Gao, Ruimin Zhang, Ruiqin Zhang
Ammonia has been a major reason of macrophyte decline in the water environment, and ammonium ion toxicity should be seen as universal, even in species frequently labeled as "NH4(+) specialists". To study the effects of high NH4(+)-N stress of ammonium ion nitrogen on tolerant submerged macrophytes and investigate the pathways of nitrogen assimilation in different organisms, Myriophyllum aquaticum was selected and treated with various concentrations of ammonium ions at different times. Increasing of ammonium concentration leads to an overall increase in incipient ammonia content in leaves and stems of plants...
May 16, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28525726/characterization-of-an-ionic-liquid-tolerant-%C3%AE-xylosidase-from-a-marine-derived-fungal-endophyte
#14
Anindita Sengupta, Angela Zabala, Si Yu Tan, Arthur Broadstock, T S Suryanarayanan, Venkat Gopalan
Ionic liquids (ILs) are used in lignocellulosic biomass (LCB) pretreatment due to their ability to disrupt the extensive hydrogen-bonding network in cellulose and hemicellulose, and thereby decrease LCB recalcitrance to subsequent enzymatic degradation. However, this approach necessitates development of a cellulases and hemicellulases that can tolerate ~20% (w/v) IL, an amount that either co-precipitates with the sugar polymers after the initial pretreatment or is typically used in single-pot biomass deconstructions...
May 19, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28524738/selexipag-a-selective-prostacyclin-receptor-agonist-in-pulmonary-arterial-hypertension-a-pharmacology-review
#15
Jesús Honorato Pérez
Pulmonary hypertension is defined by a mean pulmonary artery pressure ≥25 mm Hg at rest. Management of pulmonary arterial hypertension (PAH) includes specific drug therapy with calcium channel blockers in vasoreactive patients, or drugs approved for PAH in non-reactive patients that target the endothelin, nitric-oxide and prostacyclin pathways. Areas covered: The review covers receptor selectivity, pharmacokinetics, pharmacodynamics and adverse effects (AEs) of intravenous (IV) epoprostenol (synthetic prostacyclin); the prostacyclin analogs iloprost, beraprost, and treprostinil administered by IV, subcutaneous, inhaled or oral routes; and the oral selective prostacyclin receptor agonist selexipag...
May 19, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28524341/randomized-controlled-study-of-a-novel-triple-nitazoxanide-ntz-containing-therapeutic-regimen-versus-the-traditional-regimen-for-eradication-of-helicobacter-pylori-infection
#16
Mona Ah Shehata, Raghda Talaat, Samah Soliman, Huda Elmesseri, Shaimaa Soliman, Sherief Abd-Elsalam
BACKGROUND: Helicobacter pylori infection has become more and more resistant to conventional first-line treatment regimens. So, there is a considerable interest in evaluating new antibiotic combinations and regimens. Nitazoxanide is an anti-infective drug with demonstrated activity against protozoa and anaerobic bacteria including H. pylori. This work is designed to evaluate the efficacy and safety of a unique triple nitazoxanide-containing regimen as a treatment regimen in Egyptian patients with H...
May 19, 2017: Helicobacter
https://www.readbyqxmd.com/read/28523588/advances-in-the-development-of-janus-kinase-inhibitors-in-inflammatory-bowel-disease-future-prospects
#17
Mathurin Flamant, Josselin Rigaill, Stephane Paul, Xavier Roblin
Inflammatory bowel disease (IBD) is caused by a dysregulation of the immune system, inducing the production of proinflammatory cytokines and adhesion molecules. A better understanding of the mucosal immune response in IBD has led to the development of new drugs directed at inflammatory cytokines and leukocyte-trafficking molecules. Beyond tumor necrosis factor antagonists and anti-integrin molecules, which act by blocking the interaction between gut-specific lymphocytes and their receptor on vascular endothelium, the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway represents a new target in IBD...
May 18, 2017: Drugs
https://www.readbyqxmd.com/read/28523163/a-single-center-experience-rituximab-plus-cladribine-is-an-effective-and-safe-first-line-therapy-for-unresectable-bronchial-associated-lymphoid-tissue-lymphoma
#18
Zheng Wei, Jing Li, Zhixiang Cheng, Ling Yuan, Peng Liu
BACKGROUND: Bronchial-associated lymphoid tissue (BALT) lymphoma is a relatively rare form of B-cell non-Hodgkin lymphoma (B-NHL). To date, the standard systemic treatment for this disease is still under debate, and few data are accessible for newly diagnosed unresectable BALT lymphoma presented with advanced disease. The combination of rituximab (R) and cladribine (2-CdA) has shown some activity in indolent B-NHL, but its usage has not been tested in disseminated BALT lymphoma so far...
April 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28523111/discovery-of-orally-efficacious-tetrahydrobenzimidazoles-as-tgr5-agonists-for-type-2-diabetes
#19
Xuqing Zhang, Mark Wall, Zhihua Sui, Jack Kauffman, Cuifen Hou, Cailin Chen, Fuyong Du, Thomas Kirchner, Yin Liang, Dana L Johnson, William V Murray, Keith Demarest
We have discovered a novel series of tetrahydrobenzimidazoles 3 as TGR5 agonists. Initial structure-activity relationship studies with an assay that measured cAMP levels in murine enteroendocrine cells (STC-1 cells) led to the discovery of potent agonists with submicromolar EC50 values for mTGR5. Subsequent optimization through methylation of the 7-position of the core tetrahydrobenzimidazole ring resulted in the identification of potent agonists for both mTGR5 and hTGR5 (human enteroendocrine NCI-H716 cells)...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28523010/beneficial-soil-bacterium-pseudomonas-frederiksbergensis-os261-augments-salt-tolerance-and-promotes-red-pepper-plant-growth
#20
Poulami Chatterjee, Sandipan Samaddar, Rangasamy Anandham, Yeongyeong Kang, Kiyoon Kim, Gopal Selvakumar, Tongmin Sa
Soil salinity, being a part of natural ecosystems, is an increasing problem in agricultural soils throughout the world. Pseudomonas frederiksbergensis OS261 has already been proved to be an effective bio-inoculant for enhancing cold stress tolerance in plants, however, its effect on salt stress tolerance is unknown. The main aim of the present study was to elucidate P. frederiksbergensis OS261 mediated salt stress tolerance in red pepper. The plants were exposed to a salt stress using NaCl at the concentrations of 50, 100, and 150 mM after 12 days of transplantation, while plant growth and enzyme activity were estimated 50 days after sowing...
2017: Frontiers in Plant Science
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