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https://www.readbyqxmd.com/read/28088843/evaluating-surrogate-marker-information-using-censored-data
#1
Layla Parast, Tianxi Cai, Lu Tian
Given the long follow-up periods that are often required for treatment or intervention studies, the potential to use surrogate markers to decrease the required follow-up time is a very attractive goal. However, previous studies have shown that using inadequate markers or making inappropriate assumptions about the relationship between the primary outcome and surrogate marker can lead to inaccurate conclusions regarding the treatment effect. Currently available methods for identifying and validating surrogate markers tend to rely on restrictive model assumptions and/or focus on uncensored outcomes...
January 15, 2017: Statistics in Medicine
https://www.readbyqxmd.com/read/28088791/sinomenine-hydrochloride-inhibits-breast-cancer-metastasis-by-attenuating-inflammation-related-epithelial-mesenchymal-transition-and-cancer-stemness
#2
Xiao Li, Pingping Li, Chao Liu, Yu Ren, Xiaojiang Tang, Ke Wang, Jianjun He
Sinomenine hydrochloride (SH) has been investigated for its anti-tumor growth effect. We have previously reported that SH inhibited breast cancer cell proliferation via MAPKs signaling. However, whether SH could inhibit tumor metastasis has not been fully explored. In this study, we found that SH suppressed the metastasis potential of breast cancer cells. The wound healing and transwell assays showed that SH inhibited the migration and invasion ability of both 4T1 and MDA-MB-231 breast cancer cells. The orthotopic mouse model of 4T1 and the experimental mouse model of MDA-MB-231-luc (MDA-MB-231 cell line expressing firefly luciferase) demonstrated that SH treatment inhibited breast cancer metastasis by inhibiting epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties without obvious hepatotoxicity and renal toxicity...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088772/thrombospondin-immune-regulation-and-the-kidney
#3
Claudio Ponticelli, Hans-Joachim Anders
Most therapeutic attempts to prevent the progression of kidney diseases have been based on interventions to inhibit the production of transforming growth factor-β (TGF-β). Thrombospondins (TSPs) play an important role in activating TGF-β. In the healthy kidney, two TSPs are expressed, TSP1 and TSP2, which exert contrasting effects. While TSP1 is a major activator of TGF-β in renal cells and exerts pro-inflammatory effects both in vitro and in vivo, TSP2 lacks the ability for TGF-β activation but regulates matrix remodeling and inflammation in experimental kidney disease...
January 14, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28088759/how-accurate-are-accurate-force-fields-for-b-dna
#4
Pablo D Dans, Ivan Ivani, Adam Hospital, Guillem Portella, Carlos González, Modesto Orozco
Last generation of force-fields are raising expectations on the quality of molecular dynamics (MD) simulations of DNA, as well as to the belief that theoretical models can substitute experimental ones in several cases. However these claims are based on limited benchmarks, where MD simulations have shown the ability to reproduce already existing 'experimental models', which in turn, have an unclear accuracy to represent DNA conformation in solution. In this work we explore the ability of different force-fields to predict the structure of two new B-DNA dodecamers, determined herein by means of (1)H nuclear magnetic resonance (NMR)...
January 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28088750/continuous-minimally-invasive-alcohol-monitoring-using-microneedle-sensor-arrays
#5
A M Vinu Mohan, Joshua Ray Windmiller, Rupesh K Mishra, Joseph Wang
The present work describes an attractive skin-worn microneedle sensing device for the minimally invasive electrochemical monitoring of subcutaneous alcohol. The device consists of an assembly of pyramidal microneedle structures integrated with Pt and Ag wires, each with a microcavity opening. The microneedle aperture was modified by electropolymerizing o-phenylene diamine onto the Pt wire microtransducer, followed by the immobilization of alcohol oxidase (AOx) in an intermediate chitosan layer, along with an outer Nafion layer...
January 10, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28088735/long-non-coding-rna-ccat1-promotes-human-retinoblastoma-so-rb50-and-y79-cells-through-negative-regulation-of-mir-218-5p
#6
Hongxu Zhang, Jianguang Zhong, Zhenyu Bian, Xiang Fang, You Peng, Yongping Hu
OBJECTIVE: To investigate the regulatory role and potential mechanism of long non-coding RNAs (lncRNA) in human retinoblastoma (RB). METHODS: The lncRNA profile in RB tissues were analyzed by microarray and quantitative reverse transcription PCR (qRT-PCR). One of the identified lncRNAs (LncRNA CCAT1) was selected for further experiments. SO-RB50 and Y79 cells were transfected with negative control, siRNA targeting lncRNA CCAT1 (si-CCAT1) and si-CCAT1+miR218-5p inhibitor, respectively...
January 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28088700/chlorogenic-acid-ameliorated-concanavalin-a-induced-hepatitis-by-suppression-of-toll-like-receptor-4-signaling-in-mice
#7
Yinglin Yuan, Xia Gong, Li Zhang, Rong Jiang, Junxia Yang, Bin Wang, Jingyuan Wan
Chlorogenic acid (CGA), one of the most abundant dietary polyphenolic compounds, has been reported to exhibit anti-inflammatory ability. However, the hepatoprotective effects and molecular mechanisms of CGA on concanavalin A (Con A)-induced hepatitis have not been explored. In the present study, we found that pretreatment with CGA dose-dependently inhibited the elevation of plasma aminotransferases and alleviated hepatic pathological damage as well as hepatocyte apoptosis in Con A-exposed mice. Additionally, CGA markedly suppressed the production of serum tumor necrosis factor (TNF)-α and interferon (IFN)-γ, alleviated the infiltration of hepatic macrophages, neutrophils, and activated CD4(+) T lymphocytes in Con A-primed mice...
January 12, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28088698/metformin-enhancing-the-antitumor-efficacy-of-carboplatin-against-ehrlich-solid-carcinoma-grown-in-diabetic-mice-effect-on-igf-1-and-tumoral-expression-of-igf-1-receptors
#8
Dina M Abo-Elmatty, Eman A Ahmed, Mona K Tawfik, Seham A Helmy
Diabetes has been listed as a risk factor for various types of cancer. Cancer cell development can be promoted by increased levels of IGF-1 and hyperinsulinemia that are associated with diabetes type II. Metformin is an anti-diabetic agent and its potential antitumor impact has become the objective of numerous studies. In this vein, we hypothesize that using metformin in diabetes type II mice may synergistic with carboplatin for reducing the risk of cancer. Therefore, the study aimed to evaluate the in vivo antitumor activity of metformin against solid EAC tumor growth in female diabetic mice and its potential pro-apoptotic and anti-proliferative effects with clarification of its inconclusive biological mechanisms...
January 12, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28088677/the-relationship-between-children-s-sensitivity-to-dominant-and-non-dominant-patterns-of-lexical-stress-and-reading-accuracy
#9
Joanne Arciuli
This study reports on a new task for assessing children's sensitivity to lexical stress for words with different stress patterns and demonstrates that this task is useful in examining predictors of reading accuracy during the elementary years. In English, polysyllabic words beginning with a strong syllable exhibit the most common or dominant pattern of lexical stress (e.g., "coconut"), whereas polysyllabic words beginning with a weak syllable exhibit a less common non-dominant pattern (e.g., "banana"). The new Aliens Talking Underwater task assesses children's ability to match low-pass filtered recordings of words to pictures of objects...
January 12, 2017: Journal of Experimental Child Psychology
https://www.readbyqxmd.com/read/28088671/melatonin-attenuates-titanium-particle-induced-osteolysis-via-activation-of-wnt-%C3%AE-catenin-signaling-pathway
#10
Zichuan Ping, Xuanyang Hu, Liangliang Wang, Jiawei Shi, Yunxia Tao, Xiexing Wu, Zhenyang Hou, Xiaobin Guo, Wen Zhang, Huilin Yang, Yaozeng Xu, Zhirong Wang, Dechun Geng
: Wear debris-induced inhibition of bone regeneration and extensive bone resorption were common features in peri-prosthetic osteolysis (PPO). Here, we investigated the effect of melatonin on titanium particle-stimulated osteolysis in a murine calvariae model and mouse-mesenchymal-stem cells (mMSCs) culture system. Melatonin inhibited titanium particle-induced osteolysis and increased bone formation at osteolytic sites, confirmed by radiological and histomorphometric data. Furthermore, osteoclast numbers decreased dramatically in the low- and high-melatonin administration mice, as respectively, compared with the untreated animals...
January 11, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28088629/induction-of-hypothyroidism-during-early-postnatal-stages-triggers-a-decrease-in-cognitive-performance-by-decreasing-hippocampal-synaptic-plasticity
#11
Paulina Salazar, Pedro Cisternas, Juan Francisco Codocedo, Nibaldo C Inestrosa
Thyroid hormones are vital in the control of multiple body functions, including the correct performance of the brain. Multiple diseases are associated with thyroid gland functioning, including hypothyroidism. To date, little is known regarding the effects of the establishment of this condition at a young age on brain function. Here, we evaluated the effect of hypothyroidism in an early postnatal stage in cognitive abilities with focus on the hippocampus. In our model, hypothyroidism was induced in young rats at 21days of age using 0...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28088611/lactobacillus-paracasei-modulates-lps-induced-inflammatory-cytokine-release-by-monocyte-macrophages-via-the-up-regulation-of-negative-regulators-of-nf-kappab-signaling-in-a-tlr2-dependent-manner
#12
Ke-Yi Sun, Dong-Hua Xu, Chao Xie, Susan Plummer, James Tang, Xiao Fan Yang, Xiao Hui Ji
The application of the probiotic lactobacillus is suggested in the treatment of some inflammatory diseases of intestines due to its potential ability to attenuate inflammation. However, the mechanism is not completely understood. In PBMCs, Lactobacillus paracasei (L. Paracasei) down-regulated the LPS-induced production of TNF-α and IL-6. Using a macrophage-like differentiated THP-1 cell line induced by PMA, we investigated the effect of L. paracasei on the production of pro-inflammatory cytokines by monocyte-macrophages...
January 12, 2017: Cytokine
https://www.readbyqxmd.com/read/28088573/heat-shock-proteins-and-cancer-how-can-nanomedicine-be-harnessed
#13
REVIEW
Félix Sauvage, Samir Messaoudi, Elias Fattal, Gillian Barratt, Juliette Vergnaud-Gauduchon
Heat shock protein (hsp90) is an interesting target for cancer therapy because it is involved in the folding and stabilization of numerous proteins, including many that contribute to the development of cancer. It is part of the chaperone machinery that includes other heat shock proteins (hsp70, hsp27, hsp40) and is mainly localized in the cytosol, although many analogues or isoforms can be found in mitochondrion, endoplasmic reticulum and the cell membrane. Many potential inhibitors of hsp90 have been tested for cancer therapy but their usefulness is limited by their poor solubility in water and their ability to reach the target cells and the correct intracellular compartment...
January 11, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28088520/palmitic-acid-increases-invasiveness-of-pancreatic-cancer-cells-aspc-1-through-tlr4-ros-nf-%C3%AE%C2%BAb-mmp-9-signaling-pathway
#14
Makena J Binker-Cosen, Daniel Richards, Brenda Oliver, Herbert Y Gaisano, Marcelo G Binker, Laura I Cosen-Binker
Pancreatic cancer (PC) is an aggressive malady with proclivity for early metastasis. Overexpression of toll-like receptor 4 (TLR4) in pancreatic ductal adenocarcinoma, the most common type of pancreatic malignancy, correlates to tumor size, lymph node involvement, venous invasion and pathological stage. Lipopolysaccharides (LPS) are natural TLR4 ligands that have been shown to increase the invasive ability of PC cells. However, rapid inactivation of circulating LPS and low systemic absorption of inhaled LPS from the bronchoalveolar compartment make other agonists such as saturated fatty acids more suitable to be considered for TLR4-related cell invasiveness...
January 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28088493/apoptosis-induced-by-the-methanol-extract-of-salvia-miltiorrhiza-bunge-in-non-small-cell-lung-cancer-through-pten-mediated-inhibition-of-pi3k-akt-pathway
#15
Yin-Tao Ye, Wei Zhong, Pei Sun, Dong Wang, Chen Wang, Li-Min Hu, Jun-Qiang Qian
ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge, a well-known traditional Chinese medicinal (TCM) plant, has been used to treat cardiovascular diseases since thousands of years. Many studies have reported that the active component tanshinones displayed a variety of biological activities: antithrombous, antiplatelet aggregation, antioxidant and antitumor promoting. But the mechanism of how the active components working still need to be clarified. The anti-tumor effect of compounds of tanshinone (CTN), the methanol extract of Salvia miltiorrhiza Bunge roots, was investigated...
January 11, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28088492/pikuni-blackfeet-traditional-medicine-neuroprotective-activities-of-medicinal-plants-used-to-treat-parkinson-s-disease-related-symptoms
#16
Aurélie de Rus Jacquet, Mitali Arun Tambe, Sin Ying Ma, George P McCabe, Jay Hansford C Vest, Jean-Christophe Rochet
ETHNOPHARMACOLOGICAL RELEVANCE: Parkinson's disease (PD) is a multifactorial neurodegenerative disorder affecting 5% of the population over the age of 85 years. Current treatments primarily involve dopamine replacement therapy, which leads to temporary relief of motor symptoms but fails to slow the underlying neurodegeneration. Thus, there is a need for safe PD therapies with neuroprotective activity. In this study, we analyzed contemporary herbal medicinal practices used by members of the Pikuni-Blackfeet tribe from Western Montana to treat PD-related symptoms, in an effort to identify medicinal plants that are affordable to traditional communities and accessible to larger populations...
January 11, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28088480/sensing-membrane-curvature-in-macroautophagy
#17
REVIEW
Nathan Nguyen, Vladimir Shteyn, Thomas J Melia
In response to intracellular stress events ranging from starvation to pathogen invasion, the cell activates one or more forms of macroautophagy. The key event in these related pathways is the de novo formation of a new organelle called the autophagosome, which surrounds and sequesters either random portions of the cytoplasm or selectively targets individual intracellular challenges. Thus the autophagosome is a flexible membrane platform with dimensions that ultimately depend upon the target cargo. The intermediate membrane, termed the phagophore or isolation membrane, is a cup-like structure with a clear concave face and a highly curved rim...
January 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28088478/comparison-of-the-adjuvant-activity-of-emulsions-with-different-physicochemical-properties-on-the-antibody-response-towards-the-venom-of-west-african-carpet-viper-echis-ocellatus
#18
Juan Manuel Valverde, Karina Rodríguez, María Herrera, Álvaro Segura, Mariángela Vargas, Mauren Villalta, Mavis Montero, Jose María Gutiérrez, Guillermo León
Adjuvant emulsions are widely used to enhance the antibody response of the animals used as immunoglobulin source for producing antivenoms. Usually, the adjuvant activity of emulsions is attributed both to their ability to trigger "danger" signals from cells in which they induce death, and to form depots from which immunogens are slowly released. However, there is contradictory evidence suggesting that adjuvant activity of emulsions is independent of the dispersion type and the rate of immunogen release. In order to test how physical properties of emulsions, composed of mineral oil and water, affect their ability to enhance the antibody response towards snake venoms, we compared water-in-oil (W/O) emulsions prepared at volume ratios of 70/30, 50/50 or 30/70, a 50/50 oil-in-water (O/W) emulsion, and a water-in-oil-in-water (W/O/W) multiple emulsion...
January 11, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28088457/preformulation-characterization-stabilization-and-formulation-design-for-the-acrylodan-labeled-glucose-binding-protein-sm4-ac
#19
Neha Sahni, Rajoshi Chaudhuri, John M Hickey, Prakash Manikwar, Ajit D'Souza, Andrew Metters, Sangeeta B Joshi, C Russell Middaugh, David B Volkin
This study describes the physicochemical characterization, stabilization and formulation design of SM4-AC, an acrylodan labeled glucose/galactose binding protein for use in a continuous glucose monitoring device. The physical stability profile of SM4-AC as a function of pH and temperature was monitored using a combination of biophysical techniques and the resulting physical stability profile was visualized using an empirical phase diagram. Forced degradation chemical stability studies (Asn deamidation, Met oxidation) of SM4-AC were performed using a combination of capillary isoelectric focusing (cIEF), peptide mapping and reversed phase high performance liquid chromatography (RP-HPLC)...
January 11, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28088447/differential-binding-of-monovalent-cations-to-kcsa-deciphering-the-mechanisms-of-potassium-channel-selectivity
#20
Estefanía Montoya, M Lourdes Renart, A Marcela Giudici, José A Poveda, Asia M Fernández, Andrés Morales, José M González-Ros
This work explores whether the ion selectivity and permeation properties of a model potassium channel, KcsA, could be explained based on ion binding features. Non-permeant Na(+) or Li(+) bind with low affinity (millimolar KD's) to a single set of sites contributed by the S1 and S4 sites seen at the selectivity filter in the KcsA crystal structure. Conversely, permeant K(+), Rb(+), Tl(+) and even Cs(+) bind to two different sets of sites as their concentration increases, consistent with crystallographic evidence on the ability of permeant species to induce concentration-dependent transitions between conformational states (non-conductive and conductive) of the channel's selectivity filter...
January 11, 2017: Biochimica et Biophysica Acta
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