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https://www.readbyqxmd.com/read/28535649/-cancer-associated-fibroblasts-regulate-the-chemoresistance-of-lung-cancer-cell-line-a549-via-sdf-1-secretion
#1
F Zou, Z H Zhang, Y T Zhang, J Q Zhao, X L Zhang, C L Wen, X Y Song, W M Zhou
Objective: To investigate whether cancer-associated- fibroblasts (CAF), the key component of tumor microenvironment, regulate the chemoresistant capacity of lung cancer cell line A549 through SDF-1 secretion. Methods: Primary cell isolation techniques was used to isolate cancer-associated-fibroblasts from lung cancer patients. MTT assay was applied to determine the proliferation and chemoresistance of A549 cells. Quantative PCR was used to detect the mRNA changes of Bcl-xL. Western blotting was used to detect the protein expression of Bcl-xL...
May 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28535527/treatment-of-acute-antibody-mediated-rejection
#2
Giorgia Comai, Matteo Ravaioli, Olga Baraldi, Vania Cuna, Lorenzo Gasperoni, Giovanni Liviano D''Arcangelo, Maria Cappuccilli, Antonio D Pinna, Claudio Ronco, Gaetano La Manna
Acute antibody-mediated rejection (AMR) remains an important challenge in the field of kidney transplantation despite the advances in immunosuppressive strategies, and has been recognized as an important cause of allograft dysfunction and graft loss. The treatments of acute AMR are not standardized and poor evidence is currently available on the effectiveness of therapy regimens with combinations of drugs. Standard treatment for acute AMR is based on 3 cornerstones: removal of donor-specific antibodies (DSAs) from the bloodstream, reduction of DSAs synthesis, and inhibition of the interaction between DSAs and human leukocyte antigen antigens on donor's cells...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28535410/effect-of-enzyme-inhibition-on-perampanel-pharmacokinetics-why-study-design-matters
#3
Barry E Gidal, Rama Maganti, Antonio Laurenza, Haichen Yang, David A Verbel, Edgar Schuck, Jim Ferry
OBJECTIVES: Perampanel, a selective, noncompetitive AMPA receptor antagonist, is indicated as adjunctive therapy for the treatment of partial seizures with or without secondarily generalized seizures and primary generalized tonic-clonic seizures in patients with epilepsy aged 12years and older. In vitro studies and Phase I trials indicate that perampanel is metabolized almost exclusively by CYP3A, with an elimination half-life (t1/2) averaging approximately 105h. Understanding of pharmacokinetic (PK) interactions-enzyme inhibition or induction-and anticipating their occurrence are important for management of patients with epilepsy...
April 26, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28535241/management-of-depression-in-older-adults-a-review
#4
Rob M Kok, Charles F Reynolds
Importance: Depression in older adults is a common psychiatric disorder affecting their health-related quality of life. Major depression occurs in 2% of adults aged 55 years or older, and its prevalence rises with increasing age. In addition, 10% to 15% of older adults have clinically significant depressive symptoms, even in the absence of major depression. Observations: Depression presents with the same symptoms in older adults as it does in younger populations...
May 23, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28535103/value-frameworks-for-the-patient-provider-interaction-a-comparison-of-the-asco-value-framework-versus-nccn-evidence-blocks-in-determining-value-in-oncology
#5
Bijal Shah-Manek, Joseph S Galanto, Huong Nguyen, Robert Ignoffo
BACKGROUND: To address the rising concern about oncology drug costs, the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) recently developed unique tools to help providers and patients make informed decisions about the value of an anticancer regimen. The ASCO Value Framework (AVF) allows users to generate a net health benefit (NHB) score along with drug acquisition costs for oncology regimens that have been compared in a prospective randomized clinical trial...
June 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28534812/understanding-the-complex-patterns-observed-during-hepatitis-b-virus-therapy
#6
Andrea Carracedo Rodriguez, Matthias Chung, Stanca M Ciupe
Data from human clinical trials have shown that the hepatitis B virus (HBV) follows complex profiles, such as bi-phasic, tri-phasic, stepwise decay and rebound. We utilized a deterministic model of HBV kinetics following antiviral therapy to uncover the mechanistic interactions behind HBV dynamics. Analytical investigation of the model was used to separate the parameter space describing virus decay and rebound. Monte Carlo sampling of the parameter space was used to determine the virological, pharmacological and immunological factors that separate the bi-phasic and tri-phasic virus profiles...
May 19, 2017: Viruses
https://www.readbyqxmd.com/read/28534445/differential-expression-of-micro-rnas-and-their-predicted-targets-in-renal-cells-exposed-to-amphotericin-b-and-its-complex-with-copper-ii-ions
#7
Joanna Magdalena Gola, Barbara Strzałka-Mrozik, Celina Kruszniewska-Rajs, Jolanta Adamska, Mariusz Gagoś, Urszula Mazurek
MicroRNAs (miRNAs) have been reported to regulate essential biological processes, and their expression was shown to be affected by pathological processes and drug-induced toxicity. Amphotericin B (AmB) can cause liver and kidney injury, but a recently developed complex of AmB with copper (II) ions (AmB-Cu(2+)) exhibits a lower toxicity to human renal cells while retaining a high antifungal activity. The aim of our study was to assess AmB-Cu(2+)- induced changes in the miRNA profile of renal cells and to examine which biological processes are significantly affected by AmB-Cu(2+)...
May 23, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28534298/formulation-and-in-vitro-characterization-of-bioactive-mesoporous-silica-with-doxorubicin-and-metronidazole-intended-for-bone-treatment-and-regeneration
#8
Katarzyna Czarnobaj, Magdalena Prokopowicz, Wiesław Sawicki
The purpose of this study was to evaluate the surface mineralization activity and in vitro drug behavior potential of two forms of mesoporous silica: powder and granulate. Ordered mesoporous SiO2 powder was synthesized by surfactant-assisted sol-gel process using tetraethoxysilane as a silica precursor and hexadecyltrimethylammonium bromide as the structure-directing agent. The granulate was prepared using silica powder and ethyl cellulose as a binding agent. Metronidazole (MT)-an anti-inflammatory substance and doxorubicin hydrochloride (ChD)-an anti-cancer drug were chosen as drug models for delivery studies...
May 22, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28534261/the-role-of-drug-metabolites-in-the-inhibition-of-cytochrome-p450-enzymes
#9
Momir Mikov, Maja Đanić, Nebojša Pavlović, Bojan Stanimirov, Svetlana Goločorbin-Kon, Karmen Stankov, Hani Al-Salami
Following the drug administration, patients are exposed not only to the parent drug itself, but also to the metabolites generated by drug-metabolizing enzymes. The role of drug metabolites in cytochrome P450 (CYP) inhibition and subsequent drug-drug interactions (DDIs) have recently become a topic of considerable interest and scientific debate. The list of metabolites that were found to significantly contribute to clinically relevant DDIs is constantly being expanded and reported in the literature. New strategies have been developed for better understanding how different metabolites of a drug candidate contribute to its pharmacokinetic properties and pharmacological as well as its toxicological effects...
May 22, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28534036/highly-successful-hepatitis-c-virus-hcv-treatment-outcomes-in-human-immunodeficiency-virus-hcv-coinfected-patients-at-a-large-urban-ryan-white-clinic
#10
Manish Patel, Saira Rab, Aley G Kalapila, Alison Kyle, Ike Solomon Okosun, Lesley Miller
BACKGROUND: The introduction of direct-acting antivirals (DAAs) created a major paradigm shift in the treatment of chronic hepatitis C. Currently, there is little "real-world" data regarding hepatitis C virus (HCV) treatment outcomes in the human immunodeficiency virus (HIV)/HCV-coinfected population. METHODS: This retrospective cohort study examined HCV treatment outcomes of HIV/HCV-coinfected patients at a large, urban, Ryan White-funded clinic caring for an underserved population...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28533928/leucine-nicotinic-acid-synergy-stimulates-ampk-sirt1-signaling-and-regulates-lipid-metabolism-and-lifespan-in-caenorhabditis-elegans-and-hyperlipidemia-and-atherosclerosis-in-mice
#11
Antje Bruckbauer, Jheelam Banerjee, Quiang Cao, Xin Cui, Jia Jing, Lin Zha, Fenfen Li, Bingzhong Xue, Hang Shi, Michael B Zemel
BACKGROUND/AIMS: Nicotinic acid (NA), a lipid-lowering drug, serves as a source of NAD(+), the cofactor for Sirt1. Leucine (Leu) stimulates the AMPK/Sirt1 axis and amplifies the effects of other AMPK/Sirt1 activating compounds. Therefore, we tested the interactive effects of leucine and low dose NA on AMPK/Sirt1 signaling and downstream effects of lipid metabolism in cell culture, C. elegans and mice. METHODS: LDL-receptor knockout mice were fed an atherogenic Western diet supplemented with leucine (24 g/kg diet) and sub-therapeutic NA combinations (50 mg/kg diet and 250 mg/kg diet) or low therapeutic NA (1000 mg/kg diet) for 8 weeks to evaluate markers of hyperlipidemia and atherosclerosis...
2017: American Journal of Cardiovascular Disease
https://www.readbyqxmd.com/read/28533889/effects-of-low-dose-acetazolamide-on-exercise-performance-in-simulated-altitude
#12
Ernst Elisabeth, Gatterer Hannes, Burtscher Johannes, Faulhaber Martin, Pocecco Elena, Burtscher Martin
Preventive effects of acetazolamide (ACZ) on acute mountain sickness (AMS) are well established but effects on exercise performance at high altitude or in hypoxia have been less considered and are still inconsistent. We hypothesized that low-dose ACZ would not impair exercise performance at simulated high altitude. Thus, the aim of this study was to evaluate the interaction between low-dose ACZ and exercise performance in normobaric hypoxia. Sixteen subjects (8 males and 8 females) were randomly assigned either to receive low-dose ACZ (3×125 mg in 36 hours) or placebo...
2017: International Journal of Physiology, Pathophysiology and Pharmacology
https://www.readbyqxmd.com/read/28533886/a-case-management-of-hypertension-in-the-elderly-in-sub-sahara-africa-lessons-from-granny
#13
Ahmadou Musa Jingi, Liliane Mfeukeu Kuate, Jean Jacques Noubiap
Management of chronic disease conditions in the elderly is challenging. They usually have many co-morbidities requiring multiple drug regimens, and memory or cognitive problems that can interfere with management. Also, they sometimes have a degree of social problems as they might often live alone, and thereby cater for their daily activities with minimal assistance. Multiple drug use combined with their fragile health predispose them to adverse drug reactions, drug-drug interactions, and direct drug toxicity from overdosing...
2017: Pan African Medical Journal
https://www.readbyqxmd.com/read/28533752/protocatechuic-acid-a-phenolic-from-sansevieria-roxburghiana-leaves-suppresses-diabetic-cardiomyopathy-via-stimulating-glucose-metabolism-ameliorating-oxidative-stress-and-inhibiting-inflammation
#14
Niloy Bhattacharjee, Tarun K Dua, Ritu Khanra, Swarnalata Joardar, Ashis Nandy, Achintya Saha, Vincenzo De Feo, Saikat Dewanjee
Persistent hyperglycemia, impairment of redox status and establishment of inflammatory pathophysiology integrally play important role in the pathogenesis of diabetic cardiomyopathy (DC). Present study examined the therapeutic potential of protocatechuic acid isolated from the Sansevieria roxburghiana rhizomes against DC employing rodent model of type 2 diabetes (T2D). T2D was induced by high fat diet + a low-single dose of streptozotocin (35 mg/kg, i.p.). T2D rats exhibited significantly (p < 0.01) high fasting blood glucose level...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28533679/effect-of-epigallocatechin-3-gallate-major-ingredient-of-green-tea-on-the-pharmacokinetics-of-rosuvastatin-in-healthy-volunteers
#15
Tae-Eun Kim, Na Ha, Yunjeong Kim, Hyunsook Kim, Jae Wook Lee, Ji-Young Jeon, Min-Gul Kim
Previous in vitro studies have demonstrated the inhibitory effect of green tea on drug transporters. Because rosuvastatin, a lipid-lowering drug widely used for the prevention of cardiovascular events, is a substrate for many drug transporters, there is a possibility that there is interaction between green tea and rosuvastatin. The aim of this study was to investigate the effect of green tea on the pharmacokinetics of rosuvastatin in healthy volunteers. An open-label, three-treatment, fixed-sequence study was conducted...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28533511/cd47-surface-stability-is-sensitive-to-actin-disruption-prior-to-inclusion-within-the-band-3-macrocomplex
#16
Kathryn E Mordue, Bethan R Hawley, Timothy J Satchwell, Ashley M Toye
CD47 is an important 'marker of self' protein with multiple isoforms produced though alternative splicing that exhibit tissue-specific expression. Mature erythrocytes express CD47 isoform 2 only, with membrane stability of this version dependent on inclusion within the band 3 macrocomplex, via protein 4.2. At present a paucity of information exists regarding the associations and trafficking of the CD47 isoforms during erythropoiesis. We show that CD47 isoform 2 is the predominant version maintained at the surface of expanding and terminally differentiating erythroblasts...
May 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28533369/phosphorylated-presenilin-1-decreases-%C3%AE-amyloid-by-facilitating-autophagosome-lysosome-fusion
#17
Victor Bustos, Maria V Pulina, Ashley Bispo, Alison Lam, Marc Flajolet, Fred S Gorelick, Paul Greengard
Presenilin 1 (PS1), the catalytic subunit of the γ-secretase complex, cleaves βCTF to produce Aβ. We have shown that PS1 regulates Aβ levels by a unique bifunctional mechanism. In addition to its known role as the catalytic subunit of the γ-secretase complex, selective phosphorylation of PS1 on Ser367 decreases Aβ levels by increasing βCTF degradation through autophagy. Here, we report the molecular mechanism by which PS1 modulates βCTF degradation. We show that PS1 phosphorylated at Ser367, but not nonphosphorylated PS1, interacts with Annexin A2, which, in turn, interacts with the lysosomal N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) Vamp8...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533307/sox11-promotes-tumor-protective-microenvironment-interactions-through-cxcr4-and-fak-regulation-in-mantle-cell-lymphoma
#18
Patricia Balsas, Jara Palomero, Álvaro Eguileor, Marta Leonor Rodriguez, Maria Carmela Vegliante, Ester Planas-Rigol, Marta Sureda-Gómez, Maria C Cid, Elias Campo, Virginia Amador
SOX11 overexpression in Mantle Cell Lymphoma (MCL) has been associated with more aggresive behavior and worse outcome. However, SOX11 oncogenic pathways driving MCL tumor progression are poorly known. Here, we demonstrate that SOX11 binds to regulatory regions of two important genes for microenvironment-signals in cancer, (C-X-C motif) chemokine receptor 4 (CXCR4) and PTK2 (encoding for focal adhesion kinase (FAK)). Moreover, SOX11-positive xenograft and human primary MCL tumors overexpress cell migration and stromal stimulation gene signatures compared to their SOX11-negative counterparts...
May 22, 2017: Blood
https://www.readbyqxmd.com/read/28533240/heterocycle-thiazole-compounds-exhibit-antifungal-activity-through-increase-in-the-production-of-reactive-oxygen-species-in-cryptococcus-neoformans-cryptococcus-gattii-species-complex
#19
Nívea Pereira de Sá, Caroline Miranda de Lima, Cleudiomar Inácio Lino, Paulo Jorge Sanches Barbeira, Ludmila de Matos Baltazar, Daniel Assis Santos, Renata Barbosa de Oliveira, Eleftherios Mylonakis, Beth Burgwyn Fuchs, Susana Johann
Human cryptococcosis can occur as a primary or opportunistic infection and develops as an acute, sub-acute, or chronic systemic infection, involving different organs of the host. Given the limited therapeutic options and the occasional resistance to fluconazole, there is a need to develop novel drugs for the treatment of cryptococcosis. In this report, we describe promising thiazoles 1, 2, 3, and 4 and explore their possible modes of action against Cryptococcus. To this end, we show evidence of interference in the Cryptococcus antioxidant system...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533172/new-drug-strategies-to-tackle-viral-host-interactions-for-the-treatment-of-influenza-virus-infections
#20
REVIEW
Simonides I van de Wakker, Marcel J E Fischer, Ronald S Oosting
The influenza virus (IV) is a highly contagious virus causing seasonal global outbreaks affecting annually up to 20% of the world's population and leading to 250,000-500,000 deaths worldwide. Current vaccines have variable effectiveness, and, in particular during a pandemic outbreak, they are probably not available in the amounts needed to protect the world population. Therefore we need effective small molecule drugs to combat an IV infection and that can be produced, in case of pandemic, rapidly and in large quantities...
May 19, 2017: European Journal of Pharmacology
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