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https://www.readbyqxmd.com/read/28528519/il-6-blockade-in-the-management-of-non-infectious-uveitis
#1
Giuseppe Lopalco, Claudia Fabiani, Jurgen Sota, Orso Maria Lucherini, Gian Marco Tosi, Bruno Frediani, Florenzo Iannone, Mauro Galeazzi, Rossella Franceschini, Donato Rigante, Luca Cantarini
Several pathogenetic studies have paved the way for a newer more rational therapeutic approach to non-infectious uveitis, and treatment of different forms of immune-driven uveitis has drastically evolved in recent years after the advent of biotechnological drugs. Tumor necrosis factor-α targeted therapies, the first-line recommended biologics in uveitis, have certainly led to remarkable results in patients with non-infectious uveitis. Nevertheless, the decision-making process turns out to be extremely difficult in anti-tumor necrosis factor or multidrug-resistant cases...
May 20, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28528506/exposure-of-marine-mussels-to-diclofenac-modulation-of-prostaglandin-biosynthesis
#2
Frédérique Courant, Lauren Arpin-Pont, Bénilde Bonnefille, Sébastien Vacher, Marina Picot-Groz, Elena Gomez, Hélène Fenet
Human pharmaceuticals, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are an emerging threat to marine organisms. NSAIDs act through inhibition of cyclooxygenase (COX) conversion of arachidonic acid into prostaglandins. One experiment was carried out whereby marine mussels were exposed for 72 h to 1 and 100 μg/L diclofenac (DCF). A specific and sensitive method using liquid chromatography high-resolution tandem mass spectrometry was developed to quantify DCF in mussel tissues. The developed method could also clearly identify and quantify COX products, i...
May 21, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28528452/tumor-suppressor-protein-p53-exerts-negative-transcriptional-regulation-on-human-sodium-iodide-symporter-gene-expression-in-breast-cancer
#3
Madhura G Kelkar, Bhushan Thakur, Abhishek Derle, Sushmita Chatterjee, Pritha Ray, Abhijit De
PURPOSE: Aberrant expression of human sodium iodide symporter (NIS) in breast cancer (BC) is well documented but the transcription factors (TF) regulating its aberrant expression is poorly known. We identify the presence of three p53 binding sites on the human NIS promoter sequence by conducting genome-wide TF analysis, and further investigate their regulatory role. METHODS: The differences in transcription and translation were measured by real-time PCR, luciferase reporter assay, site-directed mutagenesis, in vivo optical imaging, and chromatin immunoprecipitation...
May 20, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28528299/selective-targeting-and-therapy-of-metastatic-and-multidrug-resistant-tumors-using-a-long-circulating-podophyllotoxin-nanoparticle
#4
Aniruddha Roy, Yucheng Zhao, Yang Yang, Andras Szeitz, Tara Klassen, Shyh-Dar Li
Treatment options for metastatic and multidrug resistant (MDR) tumors are limited, and most of the chemotherapeutic drugs exhibit low efficacy against MDR cancers. An anti-tubulin agent podophyllotoxin (PPT) displays high potency against MDR tumor cells. However, due to its poor solubility and non-specificity, PPT cannot be used systemically. We have developed a self-assembling nanoparticle dosage form for PPT (named Celludo) by covalently conjugating PPT and polyethylene glycol (PEG) to acetylated carboxymethyl cellulose (CMC-Ac) via ester linkages...
May 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28528250/antifungal-toxicity-of-linear-geranylphenol-influence-of-oxigenate-substituents
#5
Lautaro Taborga, Maximiliano Sortino, Carrasco Héctor, Estefanía Butassi, Susana Zacchino, Luis Espinoza
Twenty four linear geranylphenols were evaluated for their antifungal properties against ATCC and clinical isolates of Candida albicans and Cryptococcus neoformans. For the analysis of their antifungal behavior the compounds were grouped into two series: (i) compounds with only one geranyl substituent on the benzene ring and (ii) compounds with two geranyl moieties on the benzene ring. Results showed that compounds of series (i) present better antifungal activities than those of series (ii). In addition, within group (i) all compounds showed better activities against C...
May 17, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28528185/simvastatin-ameliorate-memory-deficits-and-inflammation-in-clinical-and-mouse-model-of-alzheimer-s-disease-via-modulating-the-expression-of-mir-106b
#6
Wenzhong Huang, Zhenyu Li, Liandong Zhao, Wei Zhao
BACKGROUND: Alzheimer's disease (AD) as a neurodegenerative brain disorder is a devastating pathology leading to disastrous cognitive impairments and dementia, and several studies have shown that AD is closely related to the inflammation, so anti-inflammatory treatment may provide therapeutic benefits. In this study, the effect of simvastatin on inflammation was investigated and the underlying mechanisms were explored. METHODS: First, we tested the effect of simvastatin on AD in clinical research...
May 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28528172/cannabis-and-pregnancy-maternal-child-health-implications-during-a-period-of-drug-policy-liberalization
#7
Katrina Mark, Mishka Terplan
Cannabis use is common and increasing among women in the United States. State policies are changing with a movement towards decriminalization and legalization. We explore the implications of cannabis liberalization for maternal and child health. Most women who use cannabis quit or cut back during pregnancy. Although women are concerned about the possible health effects of cannabis, providers do a poor job of counseling. There is a theoretical potential for cannabis to interfere with neurodevelopment, however human data have not identified any long-term or long lasting meaningful differences between children exposed in utero to cannabis and those not...
May 17, 2017: Preventive Medicine
https://www.readbyqxmd.com/read/28528134/enhancing-tumor-cell-response-to-multidrug-resistance-with-ph-sensitive-quercetin-and-doxorubicin-conjugated-multifunctional-nanoparticles
#8
Cenk Daglioglu
Classical chemotherapy uses chemotherapeutic agents as a mainstay of anticancer treatment. However, the development of multidrug resistance to chemotherapy limits the effectiveness of current cancer treatment. Nanosized bioconjugates combining a chemotherapeutic agent with a pharmacological approach may improve the curative effect of chemotherapeutic agents. Herein I addressed this issue by describing the synthesis, and testing of, pH-responsive Fe3O4@SiO2(FITC)-BTN/QUR/DOX multifunctional nanoparticles. The particles were designed to modulate resistance-mediating factors and to potentiate the efficacy of DOX against chemoresistance...
May 10, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28527822/synthesis-and-biological-evaluation-of-new-c-12-%C3%AE-%C3%AE-n-sulfamoyl-phenylamino-14-deoxy-andrographolide-derivatives-as-potent-anti-cancer-agents
#9
Sai Giridhar Sarma Kandanur, Srinivas Nanduri, Nageswara Rao Golakoti
Andrographolide, the major diterpenoidal constituent of Andrographis paniculata (Acanthaceae) and its derivatives have been reported to possess plethora of biological properties including potent anti-cancer activity. In this work, synthesis and in-vitro anti-cancer evaluation of new C-12-substituted aryl amino 14-deoxy-andrographolide derivatives (III a-f) are reported. The substitutions include various sulfonamide moieties -SO2-NH-R(1). The new derivatives (III a-e) exhibited improved cytotoxicity (GI50, TGI and LC50) compared to andrographolide (I) and the corresponding 3,14,19-O-triacetyl andrographolide (II) when evaluated against 60 NCI cell line panel...
April 13, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28527783/identification-of-novel-selective-p2y6-receptor-antagonists-by-high-throughput-screening-assay
#10
Masaaki Ito, Shin-Ichiro Egashira, Kazuki Yoshida, Tomoko Mineno, Kazuo Kumagai, Hirotatsu Kojima, Takayoshi Okabe, Tetsuo Nagano, Michio Ui, Isao Matsuoka
AIMS: The P2Y6 nucleotide receptor is widely involved in inflammatory responses, and is a promising molecular target for the treatment of inflammatory diseases. Although several P2Y6 receptor antagonists have been developed and evaluated thus far, none has successfully been developed into a therapeutic drug. In this study, we explored new promising compounds that inhibit the human P2Y6 receptor. MAIN METHODS: High-throughput screening (HTS) was used to study the effects of various compounds on human P2Y6 receptors expressed in 1321N1 human astrocytoma cells by monitoring intracellular Ca(2+) concentration ([Ca(2+)]i) levels using an FDSS7000 real-time fluorescence detector...
May 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/28527708/cortical-cytoskeleton-dynamics-regulates-plasma-membrane-calcium-atpase-isoform-2-pmca2-activity
#11
Marianela G Dalghi, Mariela Ferreira-Gomes, Nicolás Montalbetti, Alexandre Simonin, Emanuel E Strehler, Matthias A Hediger, Juan Pablo Rossi
We have previously shown that purified actin can directly bind to human plasma membrane Ca(2+) ATPase 4b (hPMCA4b) and exert a dual modulation on its Ca(2+)-ATPase activity: F-actin inhibits PMCA while short actin oligomers may contribute to PMCA activation. These studies had to be performed with purified proteins given the nature of the biophysical and biochemical approaches used. To assess whether a functional interaction between the PMCAs and the cortical cytoskeleton is of physiological relevance, we characterized this phenomenon in the context of a living cell by monitoring in real-time the changes in the cytosolic calcium levels ([Ca(2+)]CYT)...
May 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28527704/anti-madcam-antibody-pf-00547659-for-ulcerative-colitis-turandot-a-phase-2-randomised-double-blind-placebo-controlled-trial
#12
Séverine Vermeire, William J Sandborn, Silvio Danese, Xavier Hébuterne, Bruce A Salzberg, Maria Klopocka, Dino Tarabar, Tomas Vanasek, Miloš Greguš, Paul A Hellstern, Joo Sung Kim, Miles P Sparrow, Kenneth J Gorelick, Michelle Hinz, Alaa Ahmad, Vivek Pradhan, Mina Hassan-Zahraee, Robert Clare, Fabio Cataldi, Walter Reinisch
BACKGROUND: PF-00547659 is a fully human monoclonal antibody that binds to human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) to selectively reduce lymphocyte homing to the intestinal tract. We aimed to assess the efficacy and safety of PF-00547659 in patients with moderate to severe ulcerative colitis. METHODS: This phase 2, randomised, double-blind, placebo-controlled clinical trial recruited patients aged 18-65 years from 105 centres in 21 countries, with a history (≥3 months) of active ulcerative colitis extending more than 15 cm beyond the anal verge (with a total Mayo score ≥6 and a Mayo endoscopic subscore ≥2) who had failed or were intolerant to at least one conventional therapy...
May 17, 2017: Lancet
https://www.readbyqxmd.com/read/28527668/imaging-mass-spectrometry-ims-of-cortical-lipids-from-preclinical-to-severe-stages-of-alzheimer-s-disease
#13
E Gónzalez de San Román, I Manuel, M T Giralt, I Ferrer, R Rodríguez-Puertas
Alzheimer's disease (AD) is a progressive neurodegenerative disease affecting millions of patients worldwide. Previous studies have demonstrated alterations in the lipid composition of lipid extracts from plasma and brain samples of AD patients. However, there is no consensus regarding the qualitative and quantitative changes of lipids in brains from AD patients. In addition, the recent developments in imaging mass spectrometry methods are leading to a new stage in the in situ analysis of lipid species in brain tissue slices from human postmortem samples...
May 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28527169/isolated-renal-mucormycosis
#14
R Sriranga, Satyajeet Pawar, Wasim Khot, Neeraj Nischal, Manish Soneja, H A Venkatesh, Ragesh R Nair, Raj Kanna, Mehar C Sharma, S K Sharma
Mucormycosis in humans has been described as early as 1885 in literature. Isolated renal mucormycosis is rare as it has been mainly described in developing countries like India and China. It is rarer still to find this entity in immunocompetent young males without any risk factors. Specific guidelines on the treatment is not yet known but combined surgical and medical therapy is considered the best modality for its management. We describe a young male who presented with bilateral hydroureteronephrosis. He was initially treated as a case renal tuberculosis which is relatively more common in TB endemic country like ours...
April 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28527154/structure-based-classification-for-bile-salt-export-pump-bsep-inhibitors-using-comparative-structural-modeling-of-human-bsep
#15
Sankalp Jain, Melanie Grandits, Lars Richter, Gerhard F Ecker
The bile salt export pump (BSEP) actively transports conjugated monovalent bile acids from the hepatocytes into the bile. This facilitates the formation of micelles and promotes digestion and absorption of dietary fat. Inhibition of BSEP leads to decreased bile flow and accumulation of cytotoxic bile salts in the liver. A number of compounds have been identified to interact with BSEP, which results in drug-induced cholestasis or liver injury. Therefore, in silico approaches for flagging compounds as potential BSEP inhibitors would be of high value in the early stage of the drug discovery pipeline...
May 19, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28527126/polycaprolactone-based-nanoparticles-loaded-with-indomethacin-for-anti-inflammatory-therapy-from-preparation-to-ex-vivo-study
#16
Waisudin Badri, Karim Miladi, Sophie Robin, Céline Viennet, Qand Agha Nazari, Géraldine Agusti, Hatem Fessi, Abdelhamid Elaissari
PURPOSE: This work focused on the preparation of polycaprolactone based nanoparticles containing indomethacin to provide topical analgesic and anti-inflammatory effect for symptomatic treatment of inflammatory diseases. Indomethacin loaded nanoparticles are prepared for topical application to decrease indomethacin side effects and administration frequency. Oppositely to already reported works, in this research non-invasive method has been used for the enhancement of indomethacin dermal drug penetration...
May 19, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28527119/peroxide-dependent-oxidation-reactions-catalyzed-by-cyp191a1-from-mycobacterium-smegmatis
#17
Hye-Yeong Jo, Sun-Ha Park, Thien-Kim Le, Sang Hoon Ma, Donghak Kim, Taeho Ahn, Young Hee Joung, Chul-Ho Yun
OBJECTIVES: To find the catalytic activities of CYP191A1 from Mycobacterium smegmatis, in which functions of most P450s are unknown, by using a set of reductase systems, peroxides, and various substrates including fatty acids and human drugs. RESULTS: CYP191A1 was functionally expressed in Escherichia coli and purified. Its catalytic activities were examined with fatty acids, chromogenic and fluorogenic substrates, and several human P450 substrates, in the presence of six different types of electron transfer systems, such as rat NADPH-P450 reductase, Candida NADPH-P450 reductase, ferredoxin/ferredoxin reductase, putidaredoxin/putidaredoxin reductase, and peroxides (H2O2 and t-butyl hydroperoxide)...
May 19, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28527057/behavioral-therapy-emotion-and-pain-a-common-anatomical-background
#18
Lauren A-M Dahlke, Jeffrey J Sable, Frank Andrasik
Emotion and pain are closely intertwined in the brain, as the human experience of pain includes both affective and nociceptive components. Although each of these components relies on a different system in the brain, the two systems converge on the anterior cingulate and insular cortices, which interact with the prefrontal cortex and other frontal structures to influence behavior. Both emotional and physical pain elicit activity in these common areas, and conditions that affect one system (e.g., drugs, neural plasticity) may affect the function of the other-ultimately altering the experience of pain...
May 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28527032/methylone-and-mdpv-activate-autophagy-in-human-dopaminergic-sh-sy5y-cells-a-new-insight-into-the-context-of-%C3%AE-keto-amphetamines-related-neurotoxicity
#19
Maria João Valente, Cristina Amaral, Georgina Correia-da-Silva, José Alberto Duarte, Maria de Lourdes Bastos, Félix Carvalho, Paula Guedes de Pinho, Márcia Carvalho
Autophagy has an essential role in neuronal homeostasis and its dysregulation has been recently linked to neurotoxic effects of a growing list of psychoactive drugs, including amphetamines. However, the role of autophagy in β-keto amphetamine (β-KA) designer drugs-induced neurotoxicity has hitherto not been investigated. In the present study, we show that two commonly abused cathinone derivatives, 3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxypyrovalerone (MDPV), elicit morphological changes consistent with autophagy and neurodegeneration, including formation of autophagic vacuoles and neurite retraction in dopaminergic SH-SY5Y cells...
May 19, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28526827/activated-hepatic-stellate-cells-secrete-periostin-to-induce-stem-cell-like-phenotype-of-residual-hepatocellular-carcinoma-cells-after-heat-treatment
#20
Rui Zhang, Rong-Rong Yao, Jing-Huan Li, Gang Dong, Min Ma, Qiong-Dan Zheng, Dong-Mei Gao, Jie-Feng Cui, Zheng-Gang Ren, Rong-Xin Chen
Some evidences show that residual tumor after thermal ablation will progress rapidly. However, its mechanisms remain unclear. Here, we assessed whether activated HSCs could regulate stem cell-like property of residual tumor after incomplete thermal ablation to promote tumor progression. Human HCC cell lines were exposed to sublethal heat treatment to simulate the peripheral zone of thermal ablation. After residual HCC cells were cultured with conditional medium (CM) from activated HSCs, parameters of the stem cell-like phenotypes were analyzed...
May 19, 2017: Scientific Reports
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