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https://www.readbyqxmd.com/read/28426938/high-throughput-screening-to-identify-inhibitors-of-dead-box-helicase-ddx41
#1
Mariko Yoneyama-Hirozane, Mitsuyo Kondo, Shin-Ichi Matsumoto, Akiko Morikawa-Oki, Daisuke Morishita, Atsushi Nakanishi, Tomohiro Kawamoto, Masaharu Nakayama
The human DEAD (Asp-Glu-Ala-Asp) box protein DDX41, a member of the DEXDc helicase family, has nucleic acid-dependent ATPase and RNA and DNA translocase and unwinding activities. DDX41 is affected by somatic mutations in sporadic cases of myeloid neoplasms as well as in a biallelic fashion in 50% of patients with germline DDX41 mutations. The R525H mutation in DDX41 is thought to play important roles in the development of hereditary myelodysplastic syndrome and acute myelocytic leukemia. In this study, human DDX41 and its R525H mutant (R525H) were expressed in Escherichia coli and purified...
April 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28424078/interleukin-6-displays-lung-anti-inflammatory-properties-and-exerts-protective-hemodynamic-effects-in-a-double-hit-murine-acute-lung-injury
#2
Guillaume Voiriot, Keyvan Razazi, Valérie Amsellem, Jeanne Tran Van Nhieu, Shariq Abid, Serge Adnot, Armand Mekontso Dessap, Bernard Maitre
BACKGROUND: Interleukin 6 (IL-6) is a predictive factor of poor prognosis in patients with acute respiratory distress syndrome (ARDS). However, its acute pulmonary hemodynamic effects and role in lung injury have not been investigated in a clinically relevant murine model of ARDS. METHODS: We used adult C57Bl6 wild-type (WT) and IL-6 knock-out (IL-6KO) mice. The animals received intravenous recombinant human IL-6 (rHuIL-6) or vehicle followed by intratracheal lipopolysaccharide (LPS) or saline before undergoing low tidal volume mechanical ventilation (MV) for 5 h...
April 19, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28416758/synergistic-interactions-between-plk1-and-hdac-inhibitors-in-non-hodgkin-s-lymphoma-cells-occur-in-vitro-and-in-vivo-and-proceed-through-multiple-mechanisms
#3
Tri Nguyen, Rebecca Parker, Elisa Hawkins, Beata Holkova, Victor Yazbeck, Akhil Kolluri, Maciej Kmieciak, Mohamed Rahmani, Steven Grant
Interactions between the polo-like kinase 1 (PLK1) inhibitor volasertib and the histone deacetylase inhibitor (HDACI) belinostat were examined in diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) cells in vitro and in vivo. Exposure of DLBCL cells to very low concentrations of volasertib in combination with belinostat synergistically increased cell death (apoptosis). Similar interactions occurred in GC-, ABC-, double-hit DLBCL cells, MCL cells, bortezomib-resistant cells and primary lymphoma cells...
February 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28400483/somatic-and-inherited-mutations-in-primary-aldosteronism
#4
Fabio Luiz Fernandes-Rosa, Sheerazed Boulkroun, Maria-Christina Zennaro
Primary aldosteronism (PA), the most common form of secondary hypertension, is caused in the majority of cases by unilateral aldosterone producing adenoma (APA) or bilateral adrenal hyperplasia. In the last years, recurrent somatic mutations in KCNJ5, CACNA1D, ATP1A1, and ATP2B3 were proved to be associated with APA development, explaining more than 50% of sporadic APA. The identification of these mutations have allowed the establishment of a model for APA development involving modifications in the intracellular ionic equilibrium and in the regulation of cell membrane potential, leading to autonomous aldosterone overproduction...
April 11, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28398499/outcome-of-elderly-patients-with-diffuse-large-b-cell-lymphoma-treated-with-r-chop-results-from-the-uk-ncri-r-chop14v21-trial-with-combined-analysis-of-molecular-characteristics-with-the-dshnhl-ricover-60-trial
#5
A Kühnl, D Cunningham, N Counsell, E A Hawkes, W Qian, P Smith, N Chadwick, A Lawrie, P Mouncey, A Jack, C Pocock, K M Ardeshna, J Radford, A McMillan, J Davies, D Turner, A Kruger, P Johnson, J Gambell, A Rosenwald, G Ott, H Horn, M Ziepert, M Pfreundschuh, D Linch
BACKGROUND: There is an on-going debate whether 2- or 3-weekly administration of R-CHOP is the preferred first-line treatment for elderly patients with diffuse large B-cell lymphoma (DLBCL). The UK NCRI R-CHOP14v21 randomized phase 3 trial did not demonstrate a difference in outcomes between R-CHOP-14 and R-CHOP-21 in newly diagnosed DLBCL patients aged 19-88 years, but data on elderly patients have not been reported in detail so far. Here, we provide a subgroup analysis of patients ≥60 years treated on the R-CHOP14v21 trial with extended follow-up...
April 7, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28382141/overexpression-of-myc-and-bcl2-predicts-poor-prognosis-in-patients-with-extranodal-nk-t-cell-lymphoma-nasal-type
#6
Jing-Hua Wang, Xi-Wen Bi, Peng-Fei Li, Zhong-Jun Xia, Hui-Qiang Huang, Wen-Qi Jiang, Yu-Jing Zhang, Liang Wang
Background: Recently double-hit lymphoma or double protein expressor lymphoma has been identified as a distinct group of diffuse large B cell lymphoma with poor prognosis. However, the expression status, clinical and prognostic effect of combined overexpression of MYC and BCL2 in extranodal NK/T-cell lymphoma, nasal type (ENKTL) are not known. Materials and methods: Paraffin-embedded lymphoma samples from 53 patients with newly diagnosed ENKTL were studied using immunohistochemistry for MYC and BCL2, and fluorescent in situ hybridization (FISH) for MYC and BCL2 were done on 5 tissue sections with highest percentages of both MYC and BCL2 positive lymphoma cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28379189/the-role-of-c-myc-in-b-cell-lymphomas-diagnostic-and-molecular-aspects
#7
REVIEW
Lynh Nguyen, Peter Papenhausen, Haipeng Shao
c-MYC is one of the most essential transcriptional factors, regulating a diverse array of cellular functions, including proliferation, growth, and apoptosis. Dysregulation of c-MYC is essential in the pathogenesis of a number of B-cell lymphomas, but is rarely reported in T-cell lymphomas. c-MYC dysregulation induces lymphomagenesis by loss of the tight control of c-MYC expression, leading to overexpression of intact c-MYC protein, in contrast to the somatic mutations or fusion proteins seen in many other oncogenes...
April 5, 2017: Genes
https://www.readbyqxmd.com/read/28378514/donor-promiscuity-of-a-thermostable-transketolase-by-directed-evolution-efficient-complementation-of-1-deoxy-d-xylulose-5-phosphate-synthase-activity
#8
Thangavelu Saravanan, Sebastian Junker, Michael Kickstein, Sascha Hein, Marie-Kristin Link, Jan Ranglack, Samantha Witt, Marion Lorillière, Laurence Hecquet, Wolf-Dieter Fessner
Enzymes catalyzing asymmetric carboligation reactions typically show very high substrate specificity for their nucleophilic donor substrate components. Structure-guided engineering of the thermostable transketolase from Geobacillus stearothermophilus by directed in vitro evolution yielded new enzyme variants that are able to utilize pyruvate and higher aliphatic homologues as nucleophilic components for acyl transfer instead of the natural polyhydroxylated ketose phosphates or hydroxypyruvate. The single mutant H102T proved the best hit toward 3-methyl-2-oxobutyrate as donor, while the double variant H102L/H474S showed highest catalytic efficiency toward pyruvate as donor...
May 2, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28357165/persistent-afebrile-abdominal-pain-an-unusual-case-of-segmental-colitis-in-an-immunocompromised-host
#9
Ilias P Papakonstantinou, Emmanuel A Andreadis
In this report we describe a case of a 66-year-old woman who presented with right upper quadrant abdominal pain and bloody diarrhea. A workup revealed immunodeficiency, an immunologic profile with low complement levels resembling systemic lupus erythematosus, and a circumferential colonic wall lesion located in the ascending colon. After endoscopy and biopsy, the mass lesion was attributed to "double hit" diffuse large B-cell lymphoma, categorized as high grade large B-cell non-Hodgkin lymphoma according to the most recent revised 2016 World Health Organisation classification and considered to be a rare and highly aggressive tumor...
February 16, 2017: Curēus
https://www.readbyqxmd.com/read/28326081/the-smac-mimetic-bv6-improves-nk-cell-mediated-killing-of-rhabdomyosarcoma-cells-by-simultaneously-targeting-tumor-and-effector-cells
#10
Kyra Fischer, Sara Tognarelli, Stefanie Roesler, Cathinka Boedicker, Ralf Schubert, Alexander Steinle, Thomas Klingebiel, Peter Bader, Simone Fulda, Evelyn Ullrich
Rhabdomyosarcoma (RMS), the most common cancer of connective tissues in pediatrics, is often resistant to conventional therapies. One underlying mechanism of this resistance is the overexpression of Inhibitor of Apoptosis (IAP) proteins, leading to a dysfunctional cell death program within tumor cells. Smac mimetics (SM) are small molecules that can reactivate the cell death program by antagonizing IAP proteins and thereby compensating their overexpression. Here, we report that SM sensitize two RMS cell lines (RD and RH30) toward natural killer (NK) cell-mediated killing on the one hand, and increase the cytotoxic potential of NK cells on the other...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28325854/the-effect-of-diabetes-on-cortical-function-in-stroke-implications-for-post-stroke-plasticity
#11
William Huynh, Natalie Kwai, Ria Arnold, Arun V Krishnan, Cindy S-Y Lin, Steve Vucic, Matthew C Kiernan
Diabetes may impair the capacity for neuroplasticity such that patients experience a slower and poorer recovery after stroke. The current study aimed to investigate changes in cortical function in stroke patients with diabetes to determine how this comorbidity may impact post-stroke cortical plasticity and thereby functional recovery. From a cohort of 57 participants, threshold-tracking transcranial magnetic stimulation was utilised to assess cortical function over the ipsi- and contralesional hemispheres in 7 diabetic patients following an acute stroke, and compared to 12 stroke patients without diabetes...
March 21, 2017: Diabetes
https://www.readbyqxmd.com/read/28321092/refractory-double-hit-lymphoma-leukemia-in-childhood-mimicking-b-precursor-acute-lymphoblastic-leukemia-at-initial-presentation
#12
Suguru Uemura, Daiichiro Hasegawa, Takehito Yokoi, Nanako Nino, Teppei Tahara, Akihiro Tamura, Atsuro Saito, Aiko Kozaki, Kenji Kishimoto, Toshiaki Ishida, Keiichiro Kawasaki, Nobuyuki Yamamoto, Takeshi Mori, Noriyuki Nishimura, Yoshiyuki Kosaka
A 10-year-old girl was referred to our hospital with left preauricular adenopathy and gingival swelling. She was diagnosed with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) based on being positive for expressions of CD10, CD19, TdT and HLA-DR. She showed no CD20 expression at the time of diagnosis. Based on the initial diagnosis of BCP-ALL, induction chemotherapy for BCP-ALL was initiated. However, the blasts did not disappear from her peripheral blood. Bone marrow examination on day 33 identified 81...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28318085/inflammatory-double-hit-model-of-temporomandibular-joint-disorder-with-elevated-ccl2-cxcl9-cxcl10-rantes-and-behavioural-hypersensitivity-in-tnfr1-r2-mice
#13
S L McIlwrath, R Nesemeier, F Ma, H S Oz, L Zhang, K N Westlund
BACKGROUND: Patients with temporomandibular joint disorders (TMD), reactive arthritis and rheumatoid arthritis often have combined etiology of hereditary and microenvironmental factors contributing to joint pain. Multiple clinical and animal studies indicate 'double-hit' inflammatory insults can cause chronic inflammation. The first inflammatory insult primes the immune system and subsequent insults elicit amplified responses. The present 'double hit' study produced a chronic orofacial pain model in mice with genetic deletion of both TNFα receptors (TNFR1/R2-/-), investigating the main nociceptive signalling pathways in comparisons to wild type mice...
March 20, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28315787/the-synergistic-influence-of-ischemic-time-and-surgical-precision-on-acute-kidney-injury-after-robotic-partial-nephrectomy
#14
Julien Dagenais, Matt Maurice, Pascal Mouracade, Onder Kara, Ryan Nelson, Ercan Malkoc, Jihad Kaouk
OBJECTIVES: To examine the dynamic and potentially synergistic influence of warm ischemia time (WIT) and excisional volume loss (EVL) on predicted rates of post-partial acute kidney injury (AKI) across a range of tumor complexities. To investigate whether these modifiable variables sensitize the kidney to the other's damaging influence. METHODS: We retrospectively reviewed 1,245 patients between 2006 and 2016 with bilateral kidneys and enhancing renal masses in our single-institution robotic partial nephrectomy (PN) database...
March 15, 2017: Urology
https://www.readbyqxmd.com/read/28297445/implementation-of-a-double-gaussian-source-model-for-the-beamnrc-monte-carlo-code-and-its-influence-on-small-fields-dose-distributions
#15
Edgardo Doerner, Paola Caprile
The shape of the radiation source of a linac has a direct impact on the delivered dose distributions, especially in the case of small radiation fields. Traditionally, a single Gaussian source model is used to describe the electron beam hitting the target, although different studies have shown that the shape of the electron source can be better described by a mixed distribution consisting of two Gaussian components. Therefore, this study presents the implementation of a double Gaussian source model into the BEAMnrc Monte Carlo code...
September 2016: Journal of Applied Clinical Medical Physics
https://www.readbyqxmd.com/read/28281001/acute-complete-paraplegia-of-8-year-old-girl-caused-by-spinal-cord-infarction-following-minor-trauma-complicated-with-longitudinal-signal-change-of-spinal-cord
#16
Kosei Nagata, Yuji Tanaka, Hiroyuki Kanai, Yasushi Oshima
INTRODUCTION: Spinal cord infarction followed by minor trauma in pediatric patients is rare and causes serious paralysis. Fibrocartilaginous embolism (FCE) is a possible diagnosis and there have been no consecutive magnetic resonance imaging (MRI) reports. Here, we report a case of an acute complete paraplegia with spinal cord infarction and longitudinal spinal cord signal change following minor trauma in an 8-year-old girl. CASE DESCRIPTION: An 8-year-old girl presented to our hospital emergency services with total paraplegia 2 h after she hit her back and neck after doing a handstand and falling down...
March 9, 2017: European Spine Journal
https://www.readbyqxmd.com/read/28274247/gossypol-has-anti-cancer-effects-by-dual-targeting-mdm2-and-vegf-in-human-breast-cancer
#17
Jing Xiong, Jiansha Li, Qin Yang, Jun Wang, Tiefen Su, Sheng Zhou
BACKGROUND: Mouse double minute 2 (MDM2) and vascular endothelial growth factor (VEGF) are important molecules involved in tumor progression. We researched potential inhibitors that simultaneously target MDM2 and VEGF. In our recent study involving the performance of high-throughput screening with a fluorescence polarization assay, gossypol was identified as one of the top hits that inhibit protein-RNA binding activity. Because MDM2 is an RNA-binding protein and its targets include VEGF mRNA, we investigated whether gossypol has an inhibitory effect on MDM2-VEGF...
March 9, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28270865/obstructive-sleep-apnoea-hypopnoea-syndrome-in-adults-with-down-syndrome
#18
REVIEW
Elizabeth A Hill
KEY POINTS: Adults with Down syndrome are predisposed to obstructive sleep apnoea/hypopnoea syndrome (OSAHS) due to overlap between the Down syndrome phenotype and OSAHS risk factors.The prevalence of OSAHS in adults with Down syndrome is estimated at 35-42%. This is up to ten-times higher than in the general adult population.Symptoms of OSAHS, including behavioural and emotional disturbances as well as standard symptoms such as sleepiness, should be monitored as part of regular health surveillance in adults with Down syndrome...
December 2016: Breathe
https://www.readbyqxmd.com/read/28258977/different-sensitivities-of-photosystem-ii-in-green-algae-and-cyanobacteria-to-phenylurea-and-phenol-type-herbicides-effect-on-electron-donor-side
#19
Ekaterina K Yotsova, Martin A Stefanov, Anelia G Dobrikova, Emilia L Apostolova
The effects of short-term treatment with phenylurea (DCMU, isoproturon) and phenol-type (ioxynil) herbicides on the green alga Chlorella kessleri and the cyanobacterium Synechocystis salina with different organizations of photosystem II (PSII) were investigated using pulse amplitude modulated (PAM) chlorophyll fluorescence and photosynthetic oxygen evolution measured by polarographic oxygen electrodes (Clark-type and Joliot-type). The photosynthetic oxygen evolution showed stronger inhibition than the PSII photochemistry...
March 4, 2017: Zeitschrift Für Naturforschung. C, A Journal of Biosciences
https://www.readbyqxmd.com/read/28245710/diabetes-and-pulmonary-tuberculosis-a-global-overview-with-special-focus-on-the-situation-in-asian-countries-with-high-tb-dm-burden
#20
Chunlan Zheng, Minhui Hu, Feng Gao
BACKGROUND: The double burden of tuberculosis (TB) and diabetes mellitus (DM) is hitting certain Asian countries harder than other areas. In a global estimate, 15% of all TB cases could be attributable to DM, with 40% of those cases coming from India and China. Many other countries of South, East, and South-East Asia are of particular concern given their TB burdens, large projected increases in DM prevalence, and population size. OBJECTIVE: In this narrative review, we aimed to: (i) give an overall insight into the evidence on TB-DM epidemiology from high double burden Asian countries, (ii) present the evidence on bi-directional screening implementation in this region, (iii) discuss possible factors related to higher TB susceptibility of Asian diabetic patients, and (iv) identify TB-DM comorbidity treatment challenges...
2017: Global Health Action
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