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https://www.readbyqxmd.com/read/28445993/berberine-nanoparticles-protects-tubular-epithelial-cells-from-renal-ischemia-reperfusion-injury
#1
Da Xie, Yong Xu, Wang Jing, Zeng Juxiang, Li Hailun, Hu Yu, Dong-Hui Zheng, Yong-Tao Lin
Renal ischemia-reperfusion (I/R) injury is one of the most common causes of acute renal failure, the prognosis of which remains poor and there still lacks of effective therapeutics available in the clinic. This study aimed at investigating the effects of Berberine nanoparticles (BBR-NP) on the ischemia-reperfusion injury of renal tubular epithelial cells and underlying the mechanisms. Our results showed that in a rat model of renal I/R injury, BBR and BBR-NP protected renal against injury both functionally (as assessed by serum urea nitrogen and creatinine level) and morphologically (as assessed by HE staining, transmission electron microscopy and TUNEL staining) in a dose-dependent manner, with the effects of BBR-NP superior to BBR alone...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445988/specific-up-regulation-of-p21-by-a-small-active-rna-sequence-suppresses-human-colorectal-cancer-growth
#2
Lu-Lu Wang, Hui-Hui Guo, Yun Zhan, Chen-Lin Feng, Shuai Huang, Yan-Xing Han, Wen-Sheng Zheng, Jian-Dong Jiang
The double stranded small active RNA (saRNA)- p21-saRNA-322 inhibits tumor growth by stimulating the p21 gene expression. We focused our research of p21-saRNA-322 on colorectal cancer because 1) p21 down-regulation is a signature abnormality of the cancer, and 2) colorectal cancer might be a suitable target for in situ p21-saRNA-322 delivery. The goal of the present study is to learn the activity of p21-saRNA-322 in colorectal cancer. Three human colorectal cancer cell lines, HCT-116, HCT-116 (p53-/-) and HT-29 were transfected with the p21-saRNA-322...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445948/combined-mek-and-pi3-kinase-inhibition-reveals-synergy-in-targeting-thyroid-cancer-in-vitro-and-in-vivo
#3
Oussama ElMokh, Dorothée Ruffieux-Daidié, Matthias A Roelli, Amandine Stooss, Wayne A Phillips, Jürg Gertsch, Matthias S Dettmer, Roch-Philippe Charles
Anaplastic thyroid cancers and radioiodine resistant thyroid cancer are posing a major treat since surgery combined with Iodine131 therapy is ineffective on them. Small-molecule inhibitors are presenting a new hope for patients, but often lead to drug resistance in many cancers. Based on the major mutations found in thyroid cancer, we propose the combination of a MEK inhibitor and a Pi3'-kinase inhibitor in pre-clinical models. We used human thyroid cancer cell lines and genetically engineered double mutant BRAFV600E PIK3CAH1047R mice to evaluate the effect of both inhibitors separately or in combination in terms of proliferation and signaling in vitro; tumor burden, histology, cell death induction and tumor markers expression in vivo...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445940/suppression-of-allograft-rejection-by-cd8-cd122-pd-1-tregs-is-dictated-by-their-fas-ligand-initiated-killing-of-effector-t-cells-versus-fas-mediated-own-apoptosis
#4
Huazhen Liu, Yeshu Wang, Qiaohuang Zeng, Yu-Qun Zeng, Chun-Ling Liang, Feifei Qiu, Hong Nie, Zhenhua Dai
Mounting evidence has shown that naturally occurring CD8+CD122+ T cells are regulatory T cells (Tregs) that suppress both autoimmunity and alloimmunity. We have previously shown that CD8+CD122+PD-1+ Tregs not only suppress allograft rejection, but also are more potent in suppression than conventional CD4+CD25+ Tregs. However, the mechanisms underlying their suppression of alloimmunity are not well understood. In an adoptive T-cell transfer model of mice lacking lymphocytes, we found that suppression of skin allograft rejection by CD8+CD122+PD-1+ Tregs was mostly dependent on their expression of Fas ligand as either lacking Fas ligand or blocking it with antibodies largely abolished their suppression of allograft rejection mediated by transferred T cells...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445937/methylation-mediated-silencing-of-microrna-211-promotes-cell-growth-and-epithelial-to-mesenchymal-transition-through-activation-of-the-akt-%C3%AE-catenin-pathway-in-gbm
#5
Weidong Li, Xiaobo Miao, Lingling Liu, Yue Zhang, Xuejun Jin, Xiaojun Luo, Hai Gao, Xubin Deng
Aberrant expression of miR-211 has frequently been reported in cancer studies; however, its role in glioblastoma multiforme (GBM) has not been examined in detail. We investigated the function and the underlying mechanism of miR-211 in GBM. We revealed that miR-211 was downregulated in GBM tissues and cell lines. Restoration of miR-211 inhibited GBM cell growth and invasion both in vitro and in vivo. The epithelial to mesenchymal transition (EMT) phenotype was reversed when miR-211 expression was restored. HMGA2 was identified as a down-stream target of miR-211...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445844/upregulation-of-mir-142-3p-improves-drug-sensitivity-of-acute-myelogenous-leukemia-through-reducing-p-glycoprotein-and-repressing-autophagy-by-targeting-hmgb1
#6
Yuan Zhang, Yufeng Liu, Xueju Xu
miR-142-3p was reported to be downregulated in acute myelogenous leukemia (AML) and acted as a novel diagnostic marker. However, the regulatory effect of miR-142-3p on drug resistance of AML cells and its underlying mechanism have not been elucidated. Here, we found that miR-142-3p was significantly downregulated and high mobility group box 1 (HMGB1) was dramatically upregulated in AML samples and cells, as well as drug-resistant AML cells. P-gp level and autophagy were markedly enhanced in HL-60/ADR and HL-60/ATRA cells...
April 23, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28445822/identification-of-the-inactivating-factors-and-mechanisms-exerted-on-ms2-coliphage-in-concentrated-synthetic-urine
#7
Wakana Oishi, Daisuke Sano, Loic Decrey, Syunsuke Kadoya, Tamar Kohn, Naoyuki Funamizu
Volume reduction (condensation) is a key for the practical usage of human urine as a fertilizer because it enables the saving of storage space and the reduction of transportation cost. However, concentrated urine may carry infectious disease risks resulting from human pathogens frequently present in excreta, though the survival of pathogens in concentrated urine is not well understood. In this study, the inactivation of MS2 coliphage, a surrogate for single-stranded RNA human enteric viruses, in concentrated synthetic urine was investigated...
April 23, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28445772/rosiglitazone-pretreatment-influences-thrombin-induced-phagocytosis-by-rat-microglia-via-activating-ppar%C3%AE-and-cd36
#8
Qiong Mu, Likun Wang, Hang Hang, Chunfeng Liu, Guofeng Wu
OBJECTIVE: To explore the protective role of rosiglitazone against secondary brain injury after cerebral hemorrhage, we investigated the effect of rosiglitazone pretreatment on thrombin-induced microglial phagocytosis and described the molecular mechanisms involved in this process. METHODS: Primary microglial cells were obtained from the brain tissue of newborn Sprague-Dawley rats and were randomly divided into four groups: the normal, thrombin stimulation, thrombin-treated plus rosiglitazone, and thrombin-rosiglitazone plus proliferator-activated receptor-gamma (PPARγ) antagonist groups...
April 23, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28445763/myosin-rod-hypophosphorylation-and-cb-kinetics-in-papillary-muscles-from-a-tnc-a8v-ki-mouse-model
#9
Masataka Kawai, Jamie R Johnston, Tarek Karam, Li Wang, Rakesh K Singh, Jose R Pinto
The cardiac troponin C (TnC)-A8V mutation is associated with hypertrophic and restrictive cardiomyopathy (HCM and RCM) in human and mice. The residue affected lies in the N-helix, a region known to affect Ca(2+)-binding affinity to the N-terminal domain. Here we report on the functional effects of this mutation in skinned papillary muscle fibers from homozygous knock-in TnC-A8V mice. Muscle fibers from left ventricle were activated at 25°C under the ionic conditions of working cardiomyocytes. The pCa-tension relationship showed a 3× increase in Ca(2+)-sensitivity and a decrease (0...
April 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28445754/probing-the-dynamics-of-clot-bound-thrombin-at-venous-shear-rates
#10
Laura M Haynes, Thomas Orfeo, Kenneth G Mann, Stephen J Everse, Kathleen E Brummel-Ziedins
In closed system models of fibrin formation, exosite-mediated thrombin binding to fibrin contributes to clot stability and is resistant to inhibition by antithrombin/heparin while still susceptible to small, active-site inhibitors. Each molecule of fibrin can bind ∼1.6 thrombin molecules at low-affinity binding sites (Kd = 2.8 μM) and ∼0.3 molecules of thrombin at high-affinity binding sites (Kd = 0.15 μM). The goal of this study is to assess the stability of fibrin-bound thrombin under venous flow conditions and to determine both its accessibility and susceptibility to inhibition...
April 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28445735/a-design-principle-for-an-autonomous-post-translational-pattern-formation
#11
Shuhei S Sugai, Koji L Ode, Hiroki R Ueda
Previous autonomous pattern-formation models often assumed complex molecular and cellular networks. This theoretical study, however, shows that a system composed of one substrate with multisite phosphorylation and a pair of kinase and phosphatase can generate autonomous spatial information, including complex stripe patterns. All (de-)phosphorylation reactions are described with a generic Michaelis-Menten scheme, and all species freely diffuse without pre-existing gradients. Computational simulation upon >23,000,000 randomly generated parameter sets revealed the design motifs of cyclic reaction and enzyme sequestration by slow-diffusing substrates...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445657/aquatic-bird-bornavirus-associated-disease-in-free-living-canada-geese-branta-canadensis-in-the-northeastern-united-states
#12
Maureen Murray, Jianhua Guo, Ian Tizard, Samuel Jennings, H L Shivaprasad, Susan Payne, Julie C Ellis, Arnaud J Van Wettere, Kathleen M O'Brien
During the winter of 2013-14, 22 Canada geese ( Branta canadensis ) were admitted to the Wildlife Clinic at the Cummings School of Veterinary Medicine at Tufts University with nonspecific neurologic abnormalities and emaciation. Five of these geese, along with three geese that were submitted dead, were evaluated via histopathology, immunohistochemistry, and reverse transcription PCR (RT-PCR) for bornaviruses. Histopathologically, six of the eight birds had lymphoplasmacytic encephalitis. One bird, which also had encephalitis, had a dilated esophagus...
April 26, 2017: Journal of Wildlife Diseases
https://www.readbyqxmd.com/read/28445531/antagomir-451-inhibits-oxygen-glucose-deprivation-ogd-induced-huvec-necrosis-via-activating-ampk-signaling
#13
Xi Yang, Xiao-Qing He, Guo-Dong Li, Yong-Qing Xu
Oxygen glucose deprivation (OGD) application in cultured human umbilical vein endothelial cells (HUVECs) mimics ischemic injuries. AntagomiR-451, the miroRNA-451 ("miR-451") inhibitor, could activate pro-survival AMP-activated protein kinase (AMPK) signaling. In the current study, we showed that forced-expression of antagomiR-451 depleted miRNA-451 and significantly attenuated OGD-induced necrosis of HUVECs. Activation of AMPK was required for antagomiR-451-mediated pro-survival actions. AMPK inhibition, by AMPKα shRNA or dominant negative mutation, almost completely abolishedantagomiR-451-mediated HUVEC protection again OGD...
2017: PloS One
https://www.readbyqxmd.com/read/28445475/grhl3-binding-and-enhancers-rearrange-as-epidermal-keratinocytes-transition-between-functional-states
#14
Rachel Herndon Klein, Ziguang Lin, Amelia Soto Hopkin, William Gordon, Lam C Tsoi, Yun Liang, Johann E Gudjonsson, Bogi Andersen
Transcription factor binding, chromatin modifications and large scale chromatin re-organization underlie progressive, irreversible cell lineage commitments and differentiation. We know little, however, about chromatin changes as cells enter transient, reversible states such as migration. Here we demonstrate that when human progenitor keratinocytes either differentiate or migrate they form complements of typical enhancers and super-enhancers that are unique for each state. Unique super-enhancers for each cellular state link to gene expression that confers functions associated with the respective cell state...
April 26, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28445416/structure-function-model-for-kissing-loop-interactions-that-initiate-dimerization-of-ty1-rna
#15
Eric R Gamache, Jung H Doh, Justin Ritz, Alain Laederach, Stanislav Bellaousov, David H Mathews, M Joan Curcio
The genomic RNA of the retrotransposon Ty1 is packaged as a dimer into virus-like particles. The 5' terminus of Ty1 RNA harbors cis-acting sequences required for translation initiation, packaging and initiation of reverse transcription (TIPIRT). To identify RNA motifs involved in dimerization and packaging, a structural model of the TIPIRT domain in vitro was developed from single-nucleotide resolution RNA structural data. In general agreement with previous models, the first 326 nucleotides of Ty1 RNA form a pseudoknot with a 7-bp stem (S1), a 1-nucleotide interhelical loop and an 8-bp stem (S2) that delineate two long, structured loops...
April 26, 2017: Viruses
https://www.readbyqxmd.com/read/28445395/a-modified-lamb-wave-time-reversal-method-for-health-monitoring-of-composite-structures
#16
Liang Zeng, Jing Lin, Liping Huang
Because the time reversal operator of Lamb waves varies with frequency in composite structures, the reconstructed signal deviates from the input signal even in undamaged cases. The damage index captures the discrepancy between the two signals without differentiating the effects of time reversal operator from those of damage. This results in the risk of false alarm. To solve this issue, a modified time reversal method (MTRM) is proposed. In this method, the frequency dependence of the time reversal operator is compensated by two steps...
April 26, 2017: Sensors
https://www.readbyqxmd.com/read/28445312/early-progression-of-brain-atrophy-in-patients-with-anti-n-methyl-d-aspartate-receptor-encephalitis-case-reports
#17
Hiroshi Kataoka, Nobuhiro Sawa, Yasuyo Tonomura, Satoshi Ueno
BACKGROUND: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis responds to immunnotherapy, and approximately 80% of patients with this disorder fully recover or have only minor sequelae. Brain magnetic resonance imaging (MRI) does not show a specific abnormality, but some patients have progressive cerebral atrophy. The cerebral atrophy can become reversible after clinical improvement. METHODS: We describe 3 patients with diffuse cerebral atrophy (DCA) on serial brain MRI...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28445161/zerumbone-ameliorates-high-fat-diet-induced-adiposity-by-restoring-ampk-regulated-lipogenesis-and-microrna-146b-sirt1-mediated-adipogenesis
#18
Jiyun Ahn, Hyunjung Lee, Chang Hwa Jung, Won Hee Choi, Tae Youl Ha
Obesity is characterized by increased fat mass, as adipose tissue serves as a storage site for excess energy from food consumption. In obesity, altered lipid metabolism of adipose tissue, characterized by fatty acid uptake, de novo lipogenesis, and lipolysis, are induced. In this study, we examined the effect of zerumbone, a major sesquiterpene from wild ginger, on high-fat diet (HF)-induced obesity and dysregulated lipid metabolism in the white adipose tissues (WAT) of C57BL/6N mice. Dietary supplementation with zerumbone ameliorated HF-induced obesity and improved impaired lipid metabolism in WAT...
April 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445148/pkc-and-camk-ii-inhibitions-coordinately-rescue-ischemia-induced-gabaergic-neuron-dysfunction
#19
Li Huang, Chun Wang, Shidi Zhao, Rongjing Ge, Sudong Guan, Jin-Hui Wang
Cerebral ischemia leads to neuronal death for stroke, in which the imbalance between glutamatergic neurons and GABAergic neurons toward neural excitotoxicity is presumably involved. GABAergic neurons are vulnerable to pathological factors and impaired in an early stage of ischemia. The rescue of GABAergic neurons is expected to be the strategy to reserve ischemic neuronal impairment. As protein kinase C (PKC) and calmodulin-dependent protein kinase II (CaMK-II) are activated during ischemia, we have investigated whether the inhibitions of these kinases rescue the ischemic impairment of cortical GABAergic neurons...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445132/targeting-autophagic-cancer-stem-cells-to-reverse-chemoresistance-in-human-triple-negative-breast-cancer
#20
Guilhem Bousquet, Morad El Bouchtaoui, Tan Sophie, Christophe Leboeuf, Cédric de Bazelaire, Philippe Ratajczak, Sylvie Giacchetti, Anne de Roquancourt, Philippe Bertheau, Laurence Verneuil, Jean-Paul Feugeas, Marc Espié, Anne Janin
There is growing evidence for the role of cancer stem-cells in drug resistance, but with few in situ studies on human tumor samples to decipher the mechanisms by which they resist anticancer agents.Triple negative breast cancer (TNBC) is the most severe sub-type of breast cancer, occurring in younger women and associated with poor prognosis even when treated at a localized stage.We investigated here the relationship between complete pathological response after chemotherapy and breast cancer stem-cell characteristics in pre-treatment biopsies of 78 women with triple negative breast carcinoma (TNBC)...
April 7, 2017: Oncotarget
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