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https://www.readbyqxmd.com/read/28221344/chemoproteomic-profiling-and-discovery-of-protein-electrophiles-in-human-cells
#1
Megan L Matthews, Lin He, Benjamin D Horning, Erika J Olson, Bruno E Correia, John R Yates, Philip E Dawson, Benjamin F Cravatt
Activity-based protein profiling (ABPP) serves as a chemical proteomic platform to discover and characterize functional amino acids in proteins on the basis of their enhanced reactivity towards small-molecule probes. This approach, to date, has mainly targeted nucleophilic functional groups, such as the side chains of serine and cysteine, using electrophilic probes. Here we show that 'reverse-polarity' (RP)-ABPP using clickable, nucleophilic hydrazine probes can capture and identify protein-bound electrophiles in cells...
March 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28213125/reduced-bioavailable-manganese-causes-striatal-urea-cycle-pathology-in-huntington-s-disease-mouse-model
#2
Terry Jo V Bichell, Michal Wegrzynowicz, K Grace Tipps, Emma M Bradley, Michael A Uhouse, Miles Bryan, Kyle Horning, Nicole Fisher, Karrie Dudek, Timothy Halbesma, Preethi Umashanker, Andrew D Stubbs, Hunter K Holt, Gunnar F Kwakye, Andrew M Tidball, Roger J Colbran, Michael Aschner, M Diana Neely, Alba Di Pardo, Vittorio Maglione, Alexander Osmand, Aaron B Bowman
Huntington's disease (HD) is caused by a mutation in the huntingtin gene (HTT), resulting in profound striatal neurodegeneration through an unknown mechanism. Perturbations in the urea cycle have been reported in HD models and in HD patient blood and brain. In neurons, arginase is a central urea cycle enzyme, and the metal manganese (Mn) is an essential cofactor. Deficient biological responses to Mn, and reduced Mn accumulation have been observed in HD striatal mouse and cell models. Here we report in vivo and ex vivo evidence of a urea cycle metabolic phenotype in a prodromal HD mouse model...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28210414/eye-inside-out-endonasal-endoscopic-reposition-of-eye-from-nose-with-complete-vision-regainment
#3
Girish S Mishra, Sushen Harish Bhatt
Faciomaxillary and ocular trauma is a common entity in most emergency and trauma units. We came across a 68-year-old female patient with a history of bull horn injury over the right eye. Examination revealed an empty orbital socket with unreliable perception of light present. Imaging showed that the eye had displaced posteroinferomedially to be lying in the ethmoid air cells in the nasal cavity. Under nasal endoscopic guidance, the eye was reposited back into the orbital socket and conjunctival sutures were taken to stabilize the position...
March 2017: Craniomaxillofacial Trauma & Reconstruction
https://www.readbyqxmd.com/read/28205327/early-mixed-chimerism-based-preemptive-immunotherapy-in-children-undergoing-allogeneic-hematopoietic-stem-cell-transplantation-for-acute-leukemia
#4
Biljana Horn, Justin T Wahlstrom, Alexis Melton, Angela Liou, Marie Ouachee-Chardin, Gauri Sunkersett, Jennifer Willert, Jimmy Hwang, Jueleah Expose-Spencer, Mort C Cowan, Janelle Facchino, Christopher C Dvorak
This retrospective analysis comprises 10-year experience with early posttransplant mixed chimerism-based preemptive intervention. Out of 104 patients, 51 received preemptive immunotherapy. Their outcomes were similar to patients achieving full donor chimerism spontaneously. Among patients receiving intervention, 5-year event-free survival was identical in patients with and without pretransplant residual disease, respectively (68% [95% confidence interval (CI) 38-98%] vs. 69% [95% CI 54-85%] log-rank = 0.4)...
February 16, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28199982/n-acetyl-cysteine-attenuates-remifentanil-induced-postoperative-hyperalgesia-via-inhibiting-matrix-metalloproteinase-9-in-dorsal-root-ganglia
#5
Yue Liu, Yuan Ni, Wei Zhang, Yu-E Sun, Zhengliang Ma, Xiaoping Gu
Treatment of remifentanil-induced postoperative hyperalgesia (RIH) remains a clinical challenge because the mechanisms are not fully understood. Matrix metalloproteinase-9 (MMP-9) is a key component in neuroinflammation because of its facilitation of pro-inflammatory cytokine maturation. Therefore, inhibition of MMP-9 may represent a novel therapeutic approach to the treatment of RIH. Sprague-Dawley rats were randomly divided into three groups: Control, Incision and Remifentanil. A right plantar surgical incision was performed in Group Incision, and intraoperative remifentanil (0...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28197201/-three-methods-and-three-points-regulates-p38-mitogen-activated-protein-kinase-in-the-dorsal-horn-of-the-spinal-cord-in-a-rat-model-of-sciatic-nerve-injury
#6
Xin Guo, Tian-Yuan Yu, Wong Steven, Wen-Duan Jia, Chi Ma, Yan-Hong Tao, Chao Yang, Tao-Tao Lv, Shuai Wu, Meng-Qian Lu, Jia-Li Liu
Tuina is a traditional Chinese treatment for sensory disturbances caused by peripheral nerve injury and related diseases. Our previous studies showed that tuina regulates relevant regions and indices of the spinal dorsal horn using the Dian, Bo, and Rou method in Yinmen (BL37), Yanglingquan (GB34), and Weizhong (BL40). Treatment prevents muscle atrophy, protects spinal cord neurons, and promotes sciatic nerve repair. The mechanisms of action of tuina for treating peripheral nerve injury remain poorly understood...
December 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28192096/gabapentin-decreases-microglial-cells-and-reverses-bilateral-hyperalgesia-and-allodynia-in-rats-with-chronic-myositis
#7
A S Rosa, M F Freitas, I R C Rocha, M Chacur
In the present work, we investigated the antinociceptive effect of gabapentin in a chronic myositis model and its interference in spinal glial cells. Chronic myositis was induced by injection of Complete Freund Adjuvant (CFA) into the right gastrocnemius (GS) muscle of rats and tests for evaluating mechanical hyperalgesia, thermal hyperalgesia and tactile allodynia were performed. Pharmacological treatment with gabapentin was administrated intrathecally and 100μg and 200μg doses were tested. For analyzing astrocytes and microglia in the spinal cord, immunochemistry assay was performed...
February 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28187004/didymin-an-orally-active-citrus-flavonoid-for-targeting-neuroblastoma
#8
REVIEW
Sharad S Singhal, Sulabh Singhal, Preeti Singhal, Jyotsana Singhal, David Horne, Sanjay Awasthi
Neuroblastoma, a rapidly growing yet treatment responsive cancer, is the third most common cancer of children and the most common solid tumor in infants. Unfortunately, neuroblastoma that has lost p53 function often has a highly treatment-resistant phenotype leading to tragic outcomes. In the context of neuroblastoma, the functions of p53 and MYCN (which is amplified in ~25% of neuroblastomas) are integrally linked because they are mutually transcriptionally regulated, and because they together regulate the catalytic activity of RNA polymerases...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28182698/prevention-of-remifentanil-induced-postoperative-hyperalgesia-by-dexmedetomidine-via-regulating-the-trafficking-and-function-of-spinal-nmda-receptors-as-well-as-pkc-and-camkii-level-in-vivo-and-in-vitro
#9
Yuan Yuan, Zhe Sun, Yi Chen, Yuxin Zheng, Ke-Liang Xie, Ying He, Zhifen Wang, Guo-Lin Wang, Yong-Hao Yu
Remifentanil-induced secondary hyperalgesia has been demonstrated in both animal experiments and clinical trials. Enhancement of N-methyl-D-aspartate (NMDA) receptor trafficking as well as protein kinase C (PKC) and calmodulin-dependent protein kinase II (CaMKII) have been reported to be involved in the induction and maintenance of central sensitization. In the current study, it was demonstrated that dexmedetomidine could prevent remifentanil-induced hyperalgesia (RIH) via regulating spinal NMDAR-PKC-Ca2+/ CaMKII pathway in vivo and in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28174097/synthetic-2-aryl-3-piperidin-1-yl-ethyl-thiazolidin-4-ones-exhibit-selective-in%C3%A2-vitro-antitumoral-activity-and-inhibit-cancer-cell-growth-in-a-preclinical-model-of-glioblastoma-multiforme
#10
Elita F da Silveira, Juliana H Azambuja, Taíse Rosa de Carvalho, Alice Kunzler, Daniel S da Silva, Fernanda C Teixeira, Rodrigo Rodrigues, Fátima T Beira, Rita de Cássia Sant Anna Alves, Roselia M Spanevello, Wilson Cunico, Francieli M Stefanello, Ana P Horn, Elizandra Braganhol
Glioblastoma multiforme (GBM) is the worst form of primary brain tumor, which has a high rate of infiltration and resistance to radiation and chemotherapy, resulting in poor prognosis for patients. Recent studies show that thiazolidinones have a wide range of pharmacological properties including antimicrobial, anti-inflammatory, anti-oxidant and anti-tumor. Here, we investigate the effect antiglioma in vitro of a panel of sixteen synthetic 2-aryl-3-((piperidin-1-yl)ethyl)thiazolidin-4-ones where 13 of these decreased the viability of glioma cells 30-65% (100 μM) compared with controls...
February 4, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28170192/ferumoxytol-labeling-of-human-neural-progenitor-cells-for-diagnostic-cellular-tracking-in-the-porcine-spinal-cord-with-magnetic-resonance-imaging
#11
Jason J Lamanna, Juanmarco Gutierrez, Lindsey N Urquia, C Victor Hurtig, Elman Amador, Natalia Grin, Clive N Svendsen, Thais Federici, John N Oshinski, Nicholas M Boulis
We report on the diagnostic capability of magnetic resonance imaging (MRI)-based tracking of ferumoxytol-labeled human neural progenitor cells (hNPCs) transplanted into the porcine spinal cord. hNPCs prelabeled with two doses of ferumoxytol nanoparticles (hNPC-F(Low) and hNPC-F(High) ) were injected into the ventral horn of the spinal cord in healthy minipigs. Ferumoxytol-labeled grafts were tracked in vivo up to 105 days after transplantation with MRI. Injection accuracy was assessed in vivo at day 14 and was predictive of "on" or "off" target cell graft location assessed by histology...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28168303/pembrolizumab-as-first-line-therapy-for-patients-with-pd-l1-positive-advanced-non-small-cell-lung-cancer-a-phase-1-trial
#12
R Hui, E B Garon, J W Goldman, N B Leighl, M D Hellmann, A Patnaik, L Gandhi, J P Eder, M-J Ahn, L Horn, E Felip, E Carcereny, R Rangwala, G M Lubiniecki, J Zhang, K Emancipator, C Roach, N A Rizvi
No abstract text is available yet for this article.
February 7, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28156652/referral-practices-of-medical-oncologists-to-palliative-care-for-patients-with-metastatic-non-small-cell-lung-cancer-nsclc
#13
Leora Horn, Sharon E Phillips
: 108 Background: Early implementation of palliative care has shown to improve quality of life and prolong survival in pts with metastatic NSCLC. We sought to investigate the attitudes and referral practices among medical oncologists treating pts with metastatic NSCLC. METHODS: Participants were identified through the IASLC 2015 membership directory. All participants were contacted via email to complete an 18-question online survey that included demographic variables as well as questions on referral practice and attitudes regarding the role of palliative care in the treatment of metastatic NSCLC pts...
October 9, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28155064/how-to-treat-involvement-of-the-central-nervous-system-in-hemophagocytic-lymphohistiocytosis
#14
REVIEW
AnnaCarin Horne, Ronny Wickström, Michael B Jordan, E Ann Yeh, Ahmed Naqvi, Jan-Inge Henter, Gritta Janka
Central nervous system (CNS)-hemophagocytic lymphohistiocytosis (HLH) is not a disease in itself, but it is part of a systemic immune response. The vast majority of patients with CNS-HLH also have systemic HLH and a large number of patients with primary and secondary HLH have CNS involvement. Reactivations within the CNS are frequent during the course of HLH treatment and may occur concomitant with or independent of systemic relapses. It is also important to consider primary HLH as an underlying cause of "unknown CNS inflammation" as these patients may present with only CNS disease...
January 2017: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/28141782/effect-of-pregnancy-on-interferon-gamma-release-assay-and-tuberculin-skin-test-detection-of-latent-tb-infection-among-hiv-infected-women-in-a-high-burden-setting
#15
Sylvia M LaCourse, Lisa M Cranmer, Daniel Matemo, John Kinuthia, Barbra A Richardson, David J Horne, Grace John-Stewart
BACKGROUND: Peripartum immunologic changes may affect latent TB infection (LTBI) diagnostic performance among HIV-infected women. METHODS: HIV-infected women were serially-tested with tuberculin skin test (TST) and interferon gamma release assay (IGRA) (QuantiFERON® TB Gold In-tube [QFT]) in pregnancy and weeks postpartum in Kenya. Prevalence, sensitivity and agreement, and correlates of QFT/TST positivity were assessed. Quantitative QFT mitogen and M. tuberculosis antigen (Mtb-Ag) responses were compared by peripartum stage...
January 30, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28139953/identification-of-a-novel-renal-coccidian-apicomplexa-eimeriidae-from-the-great-horned-owl-bubo-virginianus-usa
#16
Jennie M Jankovsky, Mabre Brand, Richard W Gerhold
We diagnosed renal coccidiosis in two of five Great-horned Owls ( Bubo virginianus ) examined in eastern Tennessee, 2007-2013. Histopathologic examination of the kidneys revealed multifocal mild-to-moderate dilation and epithelial hyperplasia of collecting ducts. Renal collecting duct epithelial cells contained intracytoplasmic microgametocytes, macrogametocytes, and sporulating and sporulated oocysts. Renal coccidiosis in affected birds did not result in significant inflammation. Sequence analysis of the amplified partial 18S short subunit ribosomal RNA coding region from examination of formalin fixed tissue by using PCR disclosed a 93% identity to Eimeria reichenowi in GenBank, suggesting a novel Eimeria sp...
January 31, 2017: Journal of Wildlife Diseases
https://www.readbyqxmd.com/read/28132063/magnetic-resonance-imaging-guided-transplantation-of-neural-stem-cells-into-the-porcine-spinal-cord
#17
Jason J Lamanna, Lindsey N Urquia, Carl V Hurtig, Juanmarco Gutierrez, Cody Anderson, Pete Piferi, Thais Federici, John N Oshinski, Nicholas M Boulis
BACKGROUND: Cell-based therapies are a promising treatment option for traumatic, tumorigenic and degenerative diseases of the spinal cord. Transplantation into the spinal cord is achieved with intravascular, intrathecal, or direct intraparenchymal injection. The current standard for direct injection is limited by surgical invasiveness, difficulty in reinjection, and the inability to directly target anatomical or pathological landmarks. The objective of this study was to present the proof of principle for minimally invasive, percutaneous transplantation of stem cells into the spinal cord parenchyma of live minipigs under MR guidance...
January 28, 2017: Stereotactic and Functional Neurosurgery
https://www.readbyqxmd.com/read/28132018/proportion-of-never-smoker-non-small-cell-lung-cancer-patients-at-three-diverse-institutions
#18
Lorraine Pelosof, Chul Ahn, Ang Gao, Leora Horn, Alejandra Madrigales, Joan Cox, Dauphne McGavic, John D Minna, Adi F Gazdar, Joan Schiller
BACKGROUND: Approximately 10% to 15% of lung cancer cases in the United States occur in never smokers, but there has been much debate about whether this rate is increasing. To determine whether the proportion of never smokers among lung cancer cases is increasing, we conducted a retrospective study using registries from The University of Texas Southwestern Medical Center, Parkland Hospital, and Vanderbilt University. METHODS: Registries were queried for demographic information from 1990 to 2013 including sex, age, stage, and self-reported smoking history...
January 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28129131/6bio-enhances-oligonucleotide-activity-in-cells-a-potential-combinatorial-anti-androgen-receptor-therapy-in-prostate-cancer-cells
#19
Xiaowei Zhang, Daniela Castanotto, Sangkil Nam, David Horne, Cy Stein
Approximately 15%-25% of men diagnosed with prostate cancer do not survive their disease. The American Cancer Society estimated that for the year 2016 the number of prostate cancer deaths will be 26,120. Thus, there is a critical need for novel approaches to treat this deadly disease. Using high-throughput small-molecule screening, we found that the small molecule 6-bromo-indirubin-3'-oxime (6BIO) significantly improves the targeting of antisense oligonucleotides (ASOs) delivered by gymnosis (i.e., in the absence of any transfection reagents) in both the cell cytoplasm and the nucleus...
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28128448/chronic-infusion-of-sod1-g93a-astrocyte-secreted-factors-induces-spinal-motoneuron-degeneration-and-neuromuscular-dysfunction-in-healthy-rats
#20
U N Ramírez-Jarquín, F Rojas, B van Zundert, R Tapia
Amyotrophic lateral sclerosis is a fatal neurodegenerative disease and studies in vitro show that motoneuron degeneration is triggered by non-cell-autonomous mechanisms. However, whether soluble toxic factor(s) released by mutant superoxide dismutase 1 (SOD1) expressing astrocytes induces death of motoneurons and leads to motor dysfunction in vivo is not known. To directly test this, healthy adult rats were treated with conditioned media derived from primary mouse astrocytes (ACM) that express human (h) SOD1(G93A) (ACM-hG93A) via chronic osmotic pump infusion in the lumbar spinal cord...
January 27, 2017: Journal of Cellular Physiology
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