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https://www.readbyqxmd.com/read/29141226/a-pan-cancer-analysis-of-the-expression-and-clinical-relevance-of-small-nucleolar-rnas-in-human-cancer
#1
Jing Gong, Yajuan Li, Chun-Jie Liu, Yu Xiang, Chunlai Li, Youqiong Ye, Zhao Zhang, David H Hawke, Peter K Park, Lixia Diao, John A Putkey, Liuqing Yang, An-Yuan Guo, Chunru Lin, Leng Han
Increasing evidence has demonstrated that small nucleolar RNAs (snoRNAs) play important roles in tumorigenesis. We systematically investigated the expression landscape and clinical relevance of snoRNAs in >10,000 samples across 31 cancer types from The Cancer Genome Atlas. We observed overall elevated expression of snoRNAs and their ribonucleoproteins in multiple cancer types. We showed complex regulation of snoRNA expression by their host genes, copy number variation, and DNA methylation. Unsupervised clustering revealed that the snoRNA expression subtype is highly concordant with other molecular/clinical subtypes...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29140520/therapeutic-target-database-update-2018-enriched-resource-for-facilitating-bench-to-clinic-research-of-targeted-therapeutics
#2
Ying Hong Li, Chun Yan Yu, Xiao Xu Li, Peng Zhang, Jing Tang, Qingxia Yang, Tingting Fu, Xiaoyu Zhang, Xuejiao Cui, Gao Tu, Yang Zhang, Shuang Li, Fengyuan Yang, Qiu Sun, Chu Qin, Xian Zeng, Zhe Chen, Yu Zong Chen, Feng Zhu
Extensive efforts have been directed at the discovery, investigation and clinical monitoring of targeted therapeutics. These efforts may be facilitated by the convenient access of the genetic, proteomic, interactive and other aspects of the therapeutic targets. Here, we describe an update of the Therapeutic target database (TTD) previously featured in NAR. This update includes: (i) 2000 drug resistance mutations in 83 targets and 104 target/drug regulatory genes, which are resistant to 228 drugs targeting 63 diseases (49 targets of 61 drugs with patient prevalence data); (ii) differential expression profiles of 758 targets in the disease-relevant drug-targeted tissue of 12 615 patients of 70 diseases; (iii) expression profiles of 629 targets in the non-targeted tissues of 2565 healthy individuals; (iv) 1008 target combinations of 1764 drugs and the 1604 target combination of 664 multi-target drugs; (v) additional 48 successful, 398 clinical trial and 21 research targets, 473 approved, 812 clinical trial and 1120 experimental drugs, and (vi) ICD-10-CM and ICD-9-CM codes for additional 482 targets and 262 drugs against 98 disease conditions...
November 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29140409/ebolavirus-interferon-antagonists-protein-interaction-perspectives-to-combat-pathogenesis
#3
Anupam Banerjee, Abantika Pal, Debnath Pal, Pralay Mitra
Zaire ebolavirus, one of the most pathogenic species of Ebolavirus, is a significant threat to the human community being both highly infectious and lethal. The viral proteins (VPs), specifically VP24 and VP35, antagonize the interferon (IFN) proteins accountable for human immune response. Several efforts have been made to design vaccines and therapeutics drugs. However, the success is not encouraging because of limited knowledge about the binding site information of the VPs. Such limitations stem largely from the highly infectious nature of the virus that requires specialized personnel and biosafety laboratories...
November 13, 2017: Briefings in Functional Genomics
https://www.readbyqxmd.com/read/29139548/prospects-from-systems-serology-research
#4
REVIEW
Kelly B Arnold, Amy W Chung
Antibodies are highly functional glycoproteins capable of providing immune protection through multiple mechanisms, including direct pathogen neutralization and the engagement of their Fc-portions with surrounding effector immune cells and immune components that induce anti-pathogenic responses. Small modifications to multiple antibody biophysical features induced by vaccines and other therapeutic regimens can significantly alter functional immune outcomes, though it is difficult to predict which combinations confer protective immunity...
November 15, 2017: Immunology
https://www.readbyqxmd.com/read/29139089/cancer-stem-cells-in-head-and-neck-carcinomas-identification-and-possible-therapeutic-implications
#5
Elize Wolmarans, Sonja C Boy, Sulette Nel, Anne E Mercier, Michael Sean Pepper
The recurrence and/or lack of response of certain tumors to radio- and chemotherapy has been attributed to a small subpopulation of cells termed cancer stem cells (CSCs). CSCs have been identified in many tumors (including solid and hematological tumors). CSCs are characterized by their capacity for self-renewal, their ability to introduce heterogeneity within a tumor mass and its metastases, genomic instability, and their insensitivity to both radiation and chemotherapy. The latter highlights the clinical importance of studying this subpopulation since their resistance to traditional treatments may lead to metastatic disease and/or tumor relapse...
November 15, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29139031/in-vivo-analysis-of-the-anti-atrial-fibrillatory-proarrhythmic-and-cardiodepressive-profiles-of-dronedarone-as-a-guide-for-safety-pharmacological-evaluation-of-antiarrhythmic-drugs
#6
Yoshiyuki Motokawa, Yuji Nakamura, Mihoko Hagiwara-Nagasawa, Ai Goto, Koki Chiba, Nur Jaharat Lubna, Hiroko Izumi-Nakaseko, Kentaro Ando, Atsuhiko T Naito, Hiroshi Yamazaki, Atsushi Sugiyama
Anti-atrial fibrillatory, proarrhythmic and cardiodepressive profiles of dronedarone were analyzed using the halothane-anesthetized beagle dogs (n = 4) to create a standard protocol for clarifying both efficacy and adverse effects of anti-atrial fibrillatory drugs. Intravenous administration of dronedarone hydrochloride in doses of 0.3 and 3 mg/kg over 30 s attained the peak plasma concentrations of 61 and 1248 ng/mL, respectively, reflecting sub- to supra-therapeutic ones. The low dose decreased the left ventricular contraction and mean blood pressure, which were enhanced at the high dose...
November 14, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29138954/identification-of-compounds-from-palicourea-rigida-leaves-with-topical-anti-inflammatory-potential-using-experimental-models
#7
Rafael P Pinheiro, Muiara A Moraes, Bruna C S Santos, Rodrigo L Fabri, Glauciemar Del-Vechio-Vieira, Célia H Yamamoto, Ana Lúcia S M Araújo, Aílson L A Araújo, Orlando V Sousa
Palicourea rigida Kunth is traditionally used for the treatment of skin diseases, kidney pains and ovarian inflammation. Based on these traditional uses, this study evaluated the topical anti-inflammatory activity of the ethanol extract from P. rigida leaves (EEPR) and identified bioactive compounds. Ear edema was induced in Swiss mice by the topical application of Croton oil, arachidonic acid, phenol and capsaicin. Histopathological analysis and myeloperoxidase and N-acetyl-β-D-glucosaminidase activities were determined...
November 14, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/29138820/matrine-suppresses-cardiac-fibrosis-by-inhibiting-the-tgf%C3%A2-%C3%AE-smad-pathway-in-experimental-diabetic-cardiomyopathy
#8
Yong Zhang, Lei Cui, Gongchang Guan, Junkui Wang, Chuan Qiu, Tielin Yang, Yan Guo, Zhongwei Liu
Cardiac fibrosis is one of the pathological characteristics of diabetic cardiomyopathy (DbCM). Matrine treatment has proven to be effective in cases of organ fibrosis and cardiovascular diseases. In the present study, the anti-fibrosis-associated cardioprotective effects of matrine on DbCM were investigated. Rats with experimental DbCM were administered matrine orally. Cardiac functions were evaluated using invasive hemodynamic examinations. Cardiac compliance was assessed in isolated hearts. Using Sirius Red and fluorescence staining, the collagen in diabetic hearts was visualized...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138419/ivig-activates-fc%C3%AE-riib-ship1-pip3-pathway-to-stabilize-mast-cells-and-suppress-inflammation-after-ich-in-mice
#9
Gokce Yilmaz Akyol, Anatol Manaenko, Onat Akyol, Ihsan Solaroglu, Wing Mann Ho, Yan Ding, Jerry Flores, John H Zhang, Jiping Tang
Following intracerebral hemorrhage (ICH), the activation of mast cell contributes to brain inflammation and brain injury. The mast cell activation is negatively regulated by an inhibitory IgG-receptor. It's signals are mediated by SHIP (Src homology 2-containing inositol 5' phosphatase), in particular SHIP1, which activation leads to hydrolyzation of PIP3 (Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3, leading to the inhibition of calcium mobilization and to the attenuation of mast cell activation...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138341/long-non-coding-rna-neat1-regulated-by-the-egfr-pathway-contributes-to-glioblastoma-progression-through-the-wnt-%C3%AE-catenin-pathway-by-scaffolding-ezh2
#10
Qun Chen, Jinquan Cai, Qixue Wang, Yunfei Wang, Mingyang Liu, Jingxuan Yang, Junhu Zhou, Chun-Sheng Kang, Min Li, Chuanlu Jiang
PURPOSE: Long noncoding RNAs have been implicated in gliomagenesis, but their mechanisms of action are mainly undocumented. Through public glioma mRNA expression datasets, we found that NEAT1 was a potential oncogene. We systematically analyzed the clinical significance and mechanism of NEAT1 in glioblastoma. EXPERIMENTAL DESIGN: Initially, we evaluated whether NEAT1 expression levels could be regulated by EGFR pathway activity. We subsequently evaluated the effect of NEAT1 on the WNT/β-Catenin pathway and its target binding gene...
November 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29138137/the-next-frontier-head-and-neck-cancer-immunoprevention
#11
J Silvio Gutkind, Jack D Bui
Restoring T cell-mediated antitumor immunity by targeting immune checkpoint inhibitors in head and neck squamous cell carcinoma (HNSCC) results in immunomodulation and durable remissions. However, the overall response rate to these immunotherapies in HNSCC is only approximately 20%. This raises the possibility that immunologic intervention earlier in the HNSCC continuum, such as in oral premalignant lesions (OPL) could elicit an increased therapeutic response. New experimental studies suggest that immune therapies can be used for HNSCC prevention rather than therapy...
November 14, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29137939/in-silico-identification-and-in-vivo-characterization-of-small-molecule-therapeutic-hypothermia-mimetics
#12
Claire Coderch, María Díaz de Cerio, Jose María Zapico, Rafael Peláez, Ignacio M Larrayoz, Ana Ramos, Alfredo Martínez, Beatriz de Pascual-Teresa
Hypothermia has been proved to have a beneficial effect on several pathologies. CIRBP is one of the so termed cold-shock proteins involved in this process. In this work, we have detected small molecules capable of modulating the activity of CIRBP in the absence of a cold stimulus, by High Throughput Virtual Screening (HTVS) of the Diversity Set IV of the NCI and 15 compounds of our in-house data base. Fifteen compounds were selected from the HTVS to carry out a second screening through a cell-based Western blot assay...
October 31, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29137610/hemoglobin-stimulates-the-expression-of-adamts-5-and-adamts-9-by-synovial-cells-a-possible-cause-of-articular-cartilage-damage-after-intra-articular-hemorrhage
#13
Takuya Tajima, Tomohisa Sekimoto, Nami Yamaguchi, Noboru Taniguchi, Syuji Kurogi, Masugi Maruyama, Etsuo Chosa
BACKGROUND: ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) proteins play an important pathological role in matrix degeneration. Aggrecan degradation is a significant and critical event in early-stage osteoarthritis. To determine the effect of hemoglobin (Hb) on the ability of synovial tissues to produce ADAMTS family members, we examined the influence of Hb by synovial cells in an in vitro experimental system. METHODS: Synovial tissues were obtained from five young patients with meniscal injury under arthroscopic surgery...
November 14, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/29137591/surgical-anatomy-and-microvascular-surgical-technique-relevant-to-experimental-renal-transplant-in-rat-employing-aortic-and-inferior-venacaval-conduits
#14
Badri Man Shrestha, John Haylor
OBJECTIVES: Rat models of renal transplant are used to investigate immunologic processes and responses to therapeutic agents before their translation into routine clinical practice. In this study, we have described details of rat surgical anatomy and our experiences with the microvascular surgical technique relevant to renal transplant by employing donor inferior vena cava and aortic conduits. MATERIALS AND METHODS: For this study, 175 rats (151 Lewis and 24 Fisher) were used to establish the Fisher-Lewis rat model of chronic allograft injury at our institution...
November 15, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/29137366/p-but-not-e-or-l-selectin-mediated-rolling-adhesion-persistence-in-hemodynamic-flow-diverges-between-metastatic-and-leukocytic-cells
#15
Erin Elizabeth Edwards, Jaeho Oh, Ananyaveena Anilkumar, Katherine Gayle Birmingham, Susan Napier Thomas
The ability of leukocytic cells to engage selectins via rolling adhesion is critical to inflammation, but selectins are also implicated in mediating metastatic dissemination. Using a microfluidic- and flow-based cell adhesion chromatography experimental and analytical technique, we interrogated the cell-subtype differences in engagement and sustainment of rolling adhesion on P-, E-, and L-selectin-functionalized surfaces in physiological flow. Our results indicate that, particularly at low concentrations of P-selectin, metastatic but not leukocytic cells exhibit reduced rolling adhesion persistence, whereas both cell subtypes exhibited reduced persistence on L-selectin and high persistence on E-selectin, differences not revealed by flow cytometry analysis or reflected in the extent or velocity of rolling adhesion...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137301/antitumor-efficacy-of-triple-monoclonal-antibody-inhibition-of-epidermal-growth-factor-receptor-egfr-with-mm151-in-egfr-dependent-and-in-cetuximab-resistant-human-colorectal-cancer-cells
#16
Stefania Napolitano, Giulia Martini, Erika Martinelli, Carminia Maria Della Corte, Floriana Morgillo, Valentina Belli, Claudia Cardone, Nunzia Matrone, Fortunato Ciardiello, Teresa Troiani
Purpose: We investigated the effect of triple monoclonal antibody inhibition of EGFR to overcome acquired resistance to first generation of anti-EGFR inhibitors. Experimental design: MM151 is a mixture of three different monoclonal IgG1 antibodies directed toward three different, non-overlapping, epitopes of the EGFR. We performed an in vivo study by using human CRC cell lines (SW48, LIM 1215 and CACO2) which are sensitive to EGFR inhibitors, in order to evaluate the activity of MM151 as compared to standard anti-EGFR mAbs, such as cetuximab, as single agent or in a sequential strategy of combination MM151 with irinotecan (induction therapy) followed by MM151 with a selective MEK1/2 inhibitor (MEKi) (maintenance therapy)...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137270/human-mesenchymal-stem-cells-ameliorate-experimental-pulmonary-hypertension-induced-by-maternal-inflammation-and-neonatal-hyperoxia-in-rats
#17
Chung-Ming Chen, Willie Lin, Liang-Ti Huang, Hsiu-Chu Chou
Pulmonary hypertension is a critical problem in infants with bronchopulmonary dysplasia. This study determined the therapeutic effects of human mesenchymal stem cells (MSCs) on pulmonary hypertension in an animal model. Pregnant Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS, 0.5 mg/kg/day) on gestational days 20 and 21. The pups were randomly assigned to two treatment conditions: room air (RA) or an O2-enriched atmosphere. On postnatal day 5, they were intratracheally transplanted with human MSCs (3 × 10(5) and 1 × 10(6) cells) in 0...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136946/neuroprotective-effect-of-hesperetin-and-nano-hesperetin-on-recognition-memory-impairment-and-the-elevated-oxygen-stress-in-rat-model-of-alzheimer-s-disease
#18
Elham Kheradmand, Akbar Hajizadeh Moghaddam, Mahboobeh Zare
Alzheimer disease (AD) is a progressive dementia affecting a large proportion of the aging population. There is evidence that brain tissue in patients with AD is exposed to oxidative stress during the course of the disease. Hesperetin (Hst) is a natural flavonoid, which has been reported to exert various biological activities such as antioxidant and anti-inflammatory effect. The present study aimed to investigate the effects of hesperetin and nano-hesperetin on neurobehavioral activity and superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx) and catalase (CAT) enzymes activity, malondialdehyde (MDA) and glutathione (GSH) levels in hippocampal area of rats in an experimental model of AD...
November 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29136774/an-overview-of-neuroprotective-and-cognitive-enhancement-properties-of-lignans-from-schisandra-chinensis
#19
REVIEW
Kandhasamy Sowndhararajan, Ponnuvel Deepa, Minju Kim, Se Jin Park, Songmun Kim
Schisandra chinensis fruits have been traditionally used for thousands of years in Korea, China and Japan to treat various ailments. The fruits contain a variety of bioactive metabolites, especially lignan components have been reported to have various biological activities and have potential in the treatment of numerous neurodegenerative diseases. The lignans from S. chinensis are mainly grouped under dibenzocyclooctadiene lignans. Previous studies have reported that the crude extracts and the isolated pure lignan components effectively protect the neuronal cell damage and significantly enhance the cognitive performances...
November 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29136623/synergistic-effect-of-eicosapentaenoic-acid-on-antiproliferative-action-of-anticancer-drugs-in-a-cancer-cell-line-model
#20
Ayako Ogo, Sachi Miyake, Hisako Kubota, Masaharu Higashida, Hideo Matsumoto, Fusako Teramoto, Toshihiro Hirai
BACKGROUND/AIMS: It has been found experimentally and clinically that eicosapentaenoic acid (EPA) exerts an anticancer effect and that it has a minimal adverse event profile relative to other anticancer drugs. Any synergy between EPA and other anticancer drugs could be of therapeutic relevance, especially in elderly or high-risk patients. Therefore, we investigated the synergism between anticancer drugs and EPA experimentally. METHODS: EPA was coadministered in vitro with various anticancer drugs (paclitaxel, docetaxel, 5-fluorouracil and cis-diamminedichloridoplatinum[II]) to TE-1 cells, which were derived from human esophageal cancer tumors...
November 14, 2017: Annals of Nutrition & Metabolism
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