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https://www.readbyqxmd.com/read/28732386/a-phase-i-trial-of-nk-92-cells-for-refractory-hematological-malignancies-relapsing-after-autologous-hematopoietic-cell-transplantation-shows-safety-and-evidence-of-efficacy
#1
Brent A Williams, Arjun Datt Law, Bertrand Routy, Neal denHollander, Vikas Gupta, Xing-Hua Wang, Amélie Chaboureau, Sowmya Viswanathan, Armand Keating
BACKGROUND: Autologous NK cell therapy can treat a variety of malignancies, but is limited by patient-specific variations in potency and cell number expansion. In contrast, allogeneic NK cell lines can overcome many of these limitations. Cells from the permanent NK-92 line are constitutively activated, lack inhibitory receptors and appear to be safe based on two prior phase I trials. MATERIALS AND METHODS: We conducted a single-center, non-randomized, non-blinded, open-label, Phase I dose-escalation trial of irradiated NK-92 cells in adults with refractory hematological malignancies who relapsed after autologous hematopoietic cell transplantation (AHCT)...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732376/risk-factors-associated-with-fatality-of-severe-fever-with-thrombocytopenia-syndrome-a-meta-analysis
#2
Yuxin Chen, Bei Jia, Yong Liu, Rui Huang, Junhao Chen, Chao Wu
Severe fever with thrombocytopenia syndrome is an emerging life-threatening infectious disease identified in 2009. Given high case-fatality rate among patients with severe fever with thrombocytopenia syndrome, identification of the risk factors at acute phase associated with fatality is crucial for treatment. Therefore, we aimed to meta-analytically evaluate risk factors of fatal clinical outcome of severe fever with thrombocytopenia syndrome. 238 fatal cases and 873 non-fatal cases from 12 studies were included in this meta-analysis...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732370/silibinin-an-old-drug-for-hematological-disorders
#3
REVIEW
Hai Zou, Xing-Xing Zhu, Guo-Bing Zhang, Yuan Ma, Yi Wu, Dong-Sheng Huang
Silibinin (silybin), a non-toxic natural polyphenolic flavonoid, is the principal and the most biologically active component of silymarin. It is efficient in the treatment of acute and chronic liver disorders caused by toxins, drug, alcohol, hepatitis, and gall bladder disorders. Further, in our previous studies, we explored the anti-cancer efficacy in common cancers, such as lung, prostatic, colon, breast, bladder, as well as, hepatocellular carcinoma. Interestingly, silibinin is still not solely limited to the treatment of these diseases...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732359/resveratrol-inhibits-age-dependent-spontaneous-tumorigenesis-by-sirt1-mediated-post-translational-modulations-in-the-annual-fish-nothobranchius-guentheri
#4
Tingting Liu, Long Ma, Zhaodi Zheng, Fenglin Li, Shan Liu, Yingbo Xie, Guorong Li
Resveratrol, SIRT1 activator, inhibits carcinogenesis predominantly performed in transgenic animal models, orthotopic cancers of nude mice or different cancer cell lines, but its effects during process of spontaneous tumors using vertebrate models remain untested. Spontaneous liver neoplasm is an age-related disease and is inhibited by resveratrol in the annual fish Nothobranchius guentheri, which indicates that the fish can act as an excellent model to study spontaneous tumorigenesis. Totally, 175 fish were fed with resveratrol and another 175 fish for controls...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732288/lncrna-hotair-alleviates-rheumatoid-arthritis-by-targeting-mir-138-and-inactivating-nf-%C3%AE%C2%BAb-pathway
#5
Hong-Ju Zhang, Qiao-Feng Wei, Shu-Jun Wang, Hong-Jie Zhang, Xiu-Ying Zhang, Qin Geng, Yan-Hui Cui, Xiu-Hua Wang
Rheumatoid arthritis (RA) is a chronic and autoimmune-mediated inflammatory disease. We aimed to investigate the regulation of lncRNA HOTAIR in LPS-treated chondrocytes and RA mouse. Our results showed that HOTAIR expression was significantly reduced in LPS-treated chondrocytes. The HOTAIR was then over-expressed in chondrocytes by transfecting recombinant lentivirus carrying sequences encoding HOTAIR. The LPS-induced reduction of cell proliferation rate and production of two inflammatory factors interleukin (IL)-17, IL-23 were markedly inhibited...
July 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28732272/screening-of-the-open-scaffolds-collection-from-compounds-australia-identifies-a-new-chemical-entity-with-anthelmintic-activities-against-different-developmental-stages-of-the-barber-s-pole-worm-and-other-parasitic-nematodes
#6
Sarah Preston, Yaqing Jiao, Jonathan B Baell, Jennifer Keiser, Simon Crawford, Anson V Koehler, Tao Wang, Moana M Simpson, Ray M Kaplan, Karla J Cowley, Kaylene J Simpson, Andreas Hofmann, Abdul Jabbar, Robin B Gasser
The discovery and development of novel anthelmintic classes is essential to sustain the control of socioeconomically important parasitic worms of humans and animals. With the aim of offering novel, lead-like scaffolds for drug discovery, Compounds Australia released the 'Open Scaffolds' collection containing 33,999 compounds, with extensive information available on the physicochemical properties of these chemicals. In the present study, we screened 14,464 prioritised compounds from the 'Open Scaffolds' collection against the exsheathed third-stage larvae (xL3s) of Haemonchus contortus using recently developed whole-organism screening assays...
May 28, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28732195/fake-inhibitors-ampk-activation-trumps-inhibition
#7
Christopher G Langendorf, John W Scott, Bruce E Kemp
Protein kinase inhibitors have become increasingly important therapeutic drugs for the treatment of human diseases; however, resistance and off-target effects can limit their use. In this issue of Cell Chemical Biology, Ross et al. (2017) reveal a novel off-target mechanism where the Src kinase inhibitor SU6656 paradoxically primes AMPK for phosphorylation and activation by the upstream kinase LKB1.
July 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28732151/patients-attitudes-and-experiences-of-disease-modifying-anti-rheumatic-drugs-in-rheumatoid-arthritis-and-spondyloarthritis-a-qualitative-synthesis
#8
Ayano Kelly, Kathleen Tymms, David J Tunnicliffe, Daniel Sumpton, Chandima Perera, Kieran Fallon, Jonathan C Craig, Walter Abhayaratna, Allison Tong
OBJECTIVES: Non-adherence to disease-modifying anti-rheumatic drugs (DMARDS) in rheumatoid arthritis (RA) and spondyloarthritis (SpA) results in increased disease activity and symptoms and poorer quality of life. We aimed to describe patients' attitudes and experiences of DMARDs in RA and SpA to inform strategies to improve medication adherence. METHODS: Databases (MEDLINE, Embase, PsycINFO, CINAHL) were searched to January 2016. Thematic synthesis was used to analyze the findings...
July 21, 2017: Arthritis Care & Research
https://www.readbyqxmd.com/read/28732134/physical-functioning-pain-and-health-related-quality-of-life-in-adults-with-juvenile-idiopathic-arthritis-a-longitudinal-30-year-follow-up-study
#9
Anita Tollisen, Anne M Selvaag, Hanne A Aulie, Vibke Lilleby, Astrid Aasland, Anners Lerdal, Berit Flatø
OBJECTIVES: To describe physical functioning, pain, and health-related quality of life (HRQOL) in adults with Juvenile idiopathic arthritis (JIA), investigate changes over time, and identify predictors of poorer HRQOL after 30 years of disease duration. METHODS: Patients (N=176) clinically examined after 15 years were reassessed with the Health Assessment Questionnaire Disability Index (HAQ-DI), Visual Analogue Scale Pain (VAS pain) and Medical Outcome Study 36-item Short Form (SF-36) after 23 and 30 years...
July 21, 2017: Arthritis Care & Research
https://www.readbyqxmd.com/read/28732106/specific-%C3%AE-7-nicotinic-acetylcholine-receptor-agonist-ameliorates-isoproterenol-induced-cardiac-remodeling-in-mice-through-tgf-%C3%AE-1-smad3-pathway
#10
Yong-Hua Yang, Huan-Le Fang, Ming Zhao, Xiang-Lan Wei, Ning Zhang, Shun Wang, Yi Lu, Xiao-Jiang Yu, Lei Sun, Xi He, Dong-Ling Li, Jin-Jun Liu, Wei-Jin Zang
It is well-accepted that inflammation plays an important role in the development of cardiac remodeling and that therapeutic approaches targeting inflammation can inhibit cardiac remodeling. Although a large amount of evidence indicates that activation of α7 nicotinic acetylcholine receptor (α7nAChR) causes an anti-inflammatory effect, the role of α7nAChR in cardiac remodeling and the underlying mechanism have not been established. To investigate the effect of the specific α7nAChR agonist, PNU282987, on cardiac remodeling induced by isoproterenol (ISO 60 mg/kg/d) in mice, the cardiomyocyte cross-sectional area (CSA) and collagen volume fraction were evaluated by hematoxylin and eosin (HE) and Masson staining, respectively...
July 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28732066/inhibition-of-pulmonary-%C3%AE-carotene-15-15-oxygenase-expression-by-glucocorticoid-involves-ppar%C3%AE
#11
Xiaoming Gong, Raju Marisiddaiah, Lewis P Rubin
β-carotene 15,15'-oxygenase (BCO1) catalyzes the first step in the conversion of dietary provitamin A carotenoids to vitamin A. This enzyme is expressed in a variety of developing and adult tissues, suggesting that its activity may regulate local retinoid synthesis. Vitamin A and related compounds (retinoids) are critical regulators of lung epithelial development, integrity, and injury repair. A balance between the actions of retinoids and glucocorticoids (GCs) promotes normal lung development and, in particular, alveolarization...
2017: PloS One
https://www.readbyqxmd.com/read/28732065/direct-targets-of-pstat5-signalling-in-erythropoiesis
#12
Kevin R Gillinder, Hugh Tuckey, Charles C Bell, Graham W Magor, Stephen Huang, Melissa D Ilsley, Andrew C Perkins
Erythropoietin (EPO) acts through the dimeric erythropoietin receptor to stimulate proliferation, survival, differentiation and enucleation of erythroid progenitor cells. We undertook two complimentary approaches to find EPO-dependent pSTAT5 target genes in murine erythroid cells: RNA-seq of newly transcribed (4sU-labelled) RNA, and ChIP-seq for pSTAT5 30 minutes after EPO stimulation. We found 302 pSTAT5-occupied sites: ~15% of these reside in promoters while the rest reside within intronic enhancers or intergenic regions, some >100kb from the nearest TSS...
2017: PloS One
https://www.readbyqxmd.com/read/28732040/perceptions-of-arab-men-regarding-female-breast-cancer-screening-examinations-findings-from-a-middle-east-study
#13
Tam Truong Donnelly, Al-Hareth Al-Khater, Salha Bujassoum Al-Bader, Mohamed Ghaith Al-Kuwari, Mariam Ali Abdul Malik, Nabila Al-Meer, Rajvir Singh
OBJECTIVES: In the Middle East, Qatar in particular, the incidence of breast cancer has substantially increased in recent years, and is expected to double by 2030. This diagnosis also occurs at a later stage in the disease. Early detection along with proper treatment reduces radical mastectomy and mortality rates, yet only one-third of Arab women in Qatar participate in breast cancer screening (BCS) activities of any sort. Many women in the conservative Qatari society rely on male family members for support and protection...
2017: PloS One
https://www.readbyqxmd.com/read/28732012/multi-approach-metabolomics-analysis-and-artificial-simplified-phytocomplexes-reveal-cultivar-dependent-synergy-between-polyphenols-and-ascorbic-acid-in-fruits-of-the-sweet-cherry-prunus-avium-l
#14
Mauro Commisso, Martino Bianconi, Flavia Di Carlo, Stefania Poletti, Alessandra Bulgarini, Francesca Munari, Stefano Negri, Matteo Stocchero, Stefania Ceoldo, Linda Avesani, Michael Assfalg, Gianni Zoccatelli, Flavia Guzzo
Fruits of the sweet cherry (Prunus avium L.) accumulate a range of antioxidants that can help to prevent cardiovascular disease, inflammation and cancer. We tested the in vitro antioxidant activity of 18 sweet cherry cultivars collected from 12 farms in the protected geographical indication region of Marostica (Vicenza, Italy) during two growing seasons. Multiple targeted and untargeted metabolomics approaches (NMR, LC-MS, HPLC-DAD, HPLC-UV) as well as artificial simplified phytocomplexes representing the cultivars Sandra Tardiva, Sandra and Grace Star were then used to determine whether the total antioxidant activity reflected the additive effects of each compound or resulted from synergistic interactions...
2017: PloS One
https://www.readbyqxmd.com/read/28732007/a-data-driven-modeling-approach-to-identify-disease-specific-multi-organ-networks-driving-physiological-dysregulation
#15
Warren D Anderson, Danielle DeCicco, James S Schwaber, Rajanikanth Vadigepalli
Multiple physiological systems interact throughout the development of a complex disease. Knowledge of the dynamics and connectivity of interactions across physiological systems could facilitate the prevention or mitigation of organ damage underlying complex diseases, many of which are currently refractory to available therapeutics (e.g., hypertension). We studied the regulatory interactions operating within and across organs throughout disease development by integrating in vivo analysis of gene expression dynamics with a reverse engineering approach to infer data-driven dynamic network models of multi-organ gene regulatory influences...
July 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28732002/-gastrointestinal-stromal-tumor-in-young-pregnant-woman-case-report
#16
Walker Del Cid Jove Oblitas, Miguel Joseph Abril Barreda
Female patient, 28 years old, with a gestation of 14 weeks, natural and from Ilo-Moquegua. Came with a time of disease 4 days with hematemesis, melena, epigastric pain and syncope. Background of colonic resection for peritonitis due to trauma 20 years ago; upper gastrointestinal bleeding three years ago; paternal grandparents died of gastric cancer; chronic gastritis diagnosed from 19 year old. In laboratory studies hemoglobin of 9.2. In the upper gastrointestinal endoscopy was found absence of active upper gastrointestinal bleeding, a large tumor in proximal body toward greater curvature and posterior wall, 8 cm in diameter approximately, lobed appearance, with most of the mucosal surface unscathed is evidence, areas of ulceration of 2-3 mm covered with fibrin (biopsies taken), hard consistency, tent sign (positive) and cushionsign (negative)...
April 2017: Revista de Gastroenterología del Perú: órgano Oficial de la Sociedad de Gastroenterología del Perú
https://www.readbyqxmd.com/read/28731962/polymorphisms-in-cytochrome-p450-oxidoreductase-and-its-effect-on-drug-metabolism-and-efficacy
#17
Liang Gong, Cong-Min Zhang, Jin-Feng Lv, Hong-Hao Zhou, Lan Fan
Cytochrome P450 oxidoreductase (POR) has played a potential role in the metabolism of drugs and steroids by supplying electrons to microsomal cytochrome P450 (CYP) enzymes. More than 200 different POR mutations and polymorphisms causing more than 130 amino acid changes in the POR protein have been reported since 2004. A503V is a common amino acid sequence variant encoded by POR*28, whereas A287P and R457H are the most common disease-causing mutations in Europeans and Asians, respectively. Polymorphisms in the POR gene can affect POR activity, CYP-mediated drug metabolism activities, and the efficacy of several clinically used drugs...
July 20, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28731912/assessing-infant-and-maternal-readiness-for-newborn-discharge
#18
Ling Jing, Casidhe-Nicole Bethancourt, Thomas McDonagh
PURPOSE OF REVIEW: The review highlights the shift from prescribed length of stay (LOS) to mother-infant dyad readiness as the basis for making discharge decisions for healthy term newborns. We describe the components of readiness that should be considered in making the decision, focusing on infant clinical readiness, and maternal and familial readiness. RECENT FINDINGS: Although the Newborns' and Mothers' Health Protection Act of 1996 aimed to protect infants and mothers by establishing a minimum LOS, the American Academy of Pediatrics 2015 policy on newborn discharge acknowledges the shift from LOS-based to readiness-based discharge decision-making...
July 20, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28731853/hormonal-factors-in-the-control-of-the-browning-of-white-adipose-tissue
#19
REVIEW
Jiamiao Hu, Mark Christian
Adipose tissue has been historically classified into anabolic white adipose tissue (WAT) and catabolic brown adipose tissue (BAT). Recent studies have revealed the plasticity of WAT, where white adipocytes can be induced into 'brown-like' heat-producing adipocytes (BRITE or beige adipocytes). Recruiting and activating BRITE adipocytes in WAT (so-called 'browning') is believed to provide new avenues for the treatment of obesity-related diseases. A number of hormonal factors have been found to regulate BRITE adipose development and activity through autocrine, paracrine and systemic mechanisms...
July 21, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28731783/identification-of-sppl2a-inhibitors-by-multiparametric-analysis-of-a-high-content-ultra-high-throughput-screen
#20
Xian Zhang, Marjo Götte, Yvonne Ibig-Rehm, Ansgar Schuffenhauer, Marion Kamke, Dan Beisner, Danilo Guerini, Daniela Siebert, Ghislain M C Bonamy, Daniela Gabriel, Ursula Bodendorf
The intramembrane protease signal peptide peptidase-like 2a (SPPL2a) is a potential drug target for the treatment of autoimmune diseases due to an essential role in B cells and dendritic cells. To screen a library of 1.4 million compounds for inhibitors of SPPL2a, we developed an imaging assay detecting nuclear translocation of the proteolytically released cytosolic substrate fragment. The state-of-the-art hit calling approach based on nuclear translocation resulted in numerous false-positive hits, mainly interrupting intracellular protein trafficking...
July 1, 2017: SLAS Discovery
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