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https://www.readbyqxmd.com/read/29036915/stat3-but-not-hif-1%C3%AE-is-important-in-mediating-hypoxia-induced-chemoresistance-in-mda-mb-231-a-triple-negative-breast-cancer-cell-line
#1
Hoda Soleymani Abyaneh, Nidhi Gupta, Aneta Radziwon-Balicka, Paul Jurasz, John Seubert, Raymond Lai, Afsaneh Lavasanifar
Hypoxia-induced chemoresistance (HICR) is a well-recognized phenomenon, and in many experimental models, hypoxia inducible factor-1α (HIF-1α) is believed to be a key player. We aimed to better understand the mechanism underlying HICR in a triple negative breast cancer cell line, MDA-MB-231, with a focus on the role of HIF-1α. In this context, the effect of hypoxia on the sensitivity of MDA-MB-231 cells to cisplatin and their stem-like features was evaluated and the role of HIF-1α in both phenomena was assessed...
October 14, 2017: Cancers
https://www.readbyqxmd.com/read/29036543/pilot-reported-beta-blockers-identified-by-forensic-toxicology-analysis-of-postmortem-specimens
#2
Dennis V Canfield, Kurt M Dubowski, James M Whinnery, Estrella M Forster
Introduction: This study compared beta-blockers reported by pilots with the medications found by postmortem toxicology analysis of specimens received from fatal aviation accidents between 1999 and 2015. Several studies have compared drugs using the standard approach: Compare the drug found by toxicology analysis with the drug reported by the pilot. This study uniquely examined first the pilot-reported medication and then compared it to that detected by toxicology analysis. This study will serve two purposes: (i) to determine the capability of a toxicology laboratory to detect reported medications, and (ii) to identify pilots with medications below detectable limits...
September 25, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/29035832/new-insights-into-vinca-alkaloids-resistance-mechanism-and-circumvention-in-lung-cancer
#3
REVIEW
Ying Zhang, Shao-Hui Yang, Xiu-Li Guo
Nowadays, lung cancer, as a health problem in worldwide, has high mortality both in men and women. Despite advances in diagnosis and surgical techniques of lung cancer in recent decades, chemotherapy is still a fundamentally and extensively useful strategy. Vinca alkaloids are a class of important and widely used drugs in the treatment of lung cancer, targeting on the Vinca binding site at the exterior of microtubule plus ends. Either intrinsic or acquired resistance to chemotherapy of Vinca alkaloids has been a major obstacle to the treatment of lung cancer, which arose great interests in studies of understanding and overcoming resistance...
October 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29035746/the-exploration-of-endocytic-mechanisms-of-pla-peg-nanoparticles-prepared-by-coaxialtri-capillary-electrospray-template-removal-method
#4
Jiaming Chen, Lihua Cao, Yuecheng Cui, Kehua Tu, Hongjun Wang, Li-Qun Wang
The nano-sized poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) particles with core-shell structure were efficiently prepared by using coaxial tri-capillary electrospray-template removal method. The cellular uptake mechanism, intracellular distribution and exocytosis in A549 cell model of electrosprayed PLA-PEG nanoparticles were systemically studied. The drug release behavior of electrosprayed PLA-PEG nanoparticles were also investigated. Our results showed that PLA-PEG nanoparticles can be endocytosed quickly by A549 cells...
October 2, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29035735/transcriptome-profiling-identifies-genes-pathways-associated-with-experimental-resistance-to-paromomycin-in-leishmania-donovani
#5
Aditya Verma, Vasundhra Bhandari, Deepak Kumar Deep, Shyam Sundar, Jean Claude Dujardin, Ruchi Singh, Poonam Salotra
Widespread resistance towards antimony and reports of relapses following miltefosine treatment has severely affected the management of visceral leishmaniasis (VL) in the Indian subcontinent. Paromomycin (PMM), an aminoglycoside antibiotic, has been licensed for VL treatment in India in 2007. Although its use is still restricted in the field, unraveling the molecular mechanism of resistance towards PMM is the key to preserve the drug. In this study, PMM resistant lines were selected up to 100 μM of PMM in three distinct field isolates of Leishmania donovani at promastigote stage...
October 10, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29035040/orally-administrated-baker-s-yeast-beta-glucan-promotes-glucose-and-lipid-homeostasis-in-the-livers-of-ob-ob-mice
#6
Yan Cao, Ying Sun, Siwei Zou, Mengxia Li, Xiaojuan Xu
Baker's yeast glucan (BYG) has been reported to be anti-diabetic. Herein, further study on the effect of orally administrated BYG on glucose and lipid homeostasis in the livers of ob/ob mice was performed. It was found that BYG decreased the blood glucose and the hepatic glucose and lipid disorders. Western blotting analysis revealed that BYG up-regulated p-AKT and p-AMPK, and down-regulated p-Acc in the liver. Furthermore, RNA-Seq analysis indicated that BYG down-regulated genes responsible for gluconeogenesis (G6pase and Got1), fatty acid biosynthesis (Acly, Acc, Fas, etc...
October 16, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29034843/research-progress-in-reversal-of-tumor-multi-drug-resistance-via-natural-products
#7
Qi Guo, Hongyan Cao, Xianghui Qi, Huikai Li, Peizhi Ye, Zhiguo Wang, Danqiao Wang, Hua Zhou, Jingui Xue, Mingyu Sun
Multidrug resistance (MDR) occurs when a tumor develops resistance to multiple chemotherapeutic drugs, which may include antitumor drugs with different chemical structures and mechanisms. MDR limits the treatment effects of antitumor drugs, and is the main cause of chemotherapy failure. MDR is caused by numerous factors including changes in ABC transporters, target proteins, detoxification, DNA repair, drug metabolic enzymes, and signal pathways of apoptosis. Clinical research indicates that natural products have great potential to treat tumors and reverse MDR...
October 16, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29034836/nanomedicine-for-intranasal-delivery-to-improve-brain-uptake
#8
Amit A Patel, Ravish J Patel, Shachi R Patel
Intranasal drug delivery system provide distinct advantage over conventional drug delivery system for a drug that is pharmacokenetically or biologically unstable. Major concern for treatment of central nervous system diseases are law concentration of therapeutically active molecule within brain as blood brain barrier is creating obstacle, where intranasal drug delivery provides direct transport of therapeutically active moiety into brain via olfactory or trigeminal pathway. Nasal mucosa provides distinct advantage like improved bioavailability, law dose and quick onset of action and high patient compliance, major disadvantage is residence time of drug and irreversible entrapment of drug...
October 13, 2017: Current Drug Delivery
https://www.readbyqxmd.com/read/29034773/substrate-dependent-effects-of-molecular-targeted-anticancer-agents-on-activity-of-organic-anion-transporting-polypeptide-1b1
#9
Hiroyoshi Koide, Masayuki Tsujimoto, Ai Takeuchi, Miyu Tanaka, Yoko Ikegami, Mayu Tagami, Syoko Abe, Miki Hashimoto, Tetsuya Minegaki, Kohshi Nishiguchi
1. Organic anion-transporting polypeptide 1B1 (OATP1B1) plays an important role in the hepatic uptake of a broad range of substrate drugs. In vitro experiments show that molecular-targeted agents do not always have similar effects on OATP1B1 activity. 2. The purpose of this study was to clarify whether the effects of molecular-targeted agents on OATP1B1 are substrate-dependent. We used OATP1B1-transfected cells to compare the effects of molecular-targeted agents on OATP1B1-mediated uptake of fluorescein (FL), 2',7'-dichlorofluorescein (DCF), atorvastatin, SN-38, and valsartan...
October 16, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29033828/perspective-insights-of-exosomes-in-neurodegenerative-diseases-a-critical-appraisal
#10
REVIEW
Arif Tasleem Jan, Mudasir A Malik, Safikur Rahman, Hye R Yeo, Eun J Lee, Tasduq S Abdullah, Inho Choi
Exosomes are small membranous entities of endocytic origin. Their production by a wide variety of cells in eukaryotes implicates their roles in the execution of essential processes, especially cellular communication. Exosomes are secreted under both physiological and pathophysiological conditions, and their actions on neighboring and distant cells lead to the modulations of cellular behaviors. They also assist in the delivery of disease causing entities, such as prions, α-syn, and tau, and thus, facilitate spread to non-effected regions and accelerate the progressions of neurodegenerative diseases...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29033796/laminar-and-cellular-distribution-of-monoamine-receptors-in-rat-medial-prefrontal-cortex
#11
REVIEW
Noemí Santana, Francesc Artigas
The prefrontal cortex (PFC) is deeply involved in higher brain functions, many of which are altered in psychiatric conditions. The PFC exerts a top-down control of most cortical and subcortical areas through descending pathways and is densely innervated by axons emerging from the brainstem monoamine cell groups, namely, the dorsal and median raphe nuclei (DR and MnR, respectively), the ventral tegmental area and the locus coeruleus (LC). In turn, the activity of these cell groups is tightly controlled by afferent pathways arising from layer V PFC pyramidal neurons...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/29032766/the-effects-of-drug-metabolizing-enzyme-inhibitors-on-hepatic-efflux-and-uptake-transporters
#12
Jonathan Cheong, Jason S Halladay, Jasleen K Sodhi, Emile Plise, Laurent Salphati
BACKGROUND: Non-selective chemical inhibitors of phase I and phase II enzymes are commonly used in in vitro metabolic studies to elucidate the biotransformation pathways of drugs. However, the inhibition of the inhibitors on efflux and uptake transporters is not well investigated, potentially leading to unexpected and ambiguous results in these studies. OBJECTIVE: The commonly used metabolizing enzyme inhibitors, 1-aminobenzotriazole (ABT), SKF-525A, pargyline, allopurinol, menadione, methimazole, piperine and raloxifene, were examined for their potential inhibition of the major hepatic ABC (ATP binding cassette) and SLC (solute carrier) transporters...
October 10, 2017: Drug Metabolism Letters
https://www.readbyqxmd.com/read/29032638/sodium-glucose-co-transporter-2-inhibitor-tofogliflozin-shows-better-improvements-of-blood-glucose-and-insulin-secretion-in-patients-with-high-insulin-levels-at-baseline
#13
Kazuyuki Tobe, Hideki Suganami, Kohei Kaku
INTRODUCTION: Sodium glucose co-transporter 2 (SGLT2) inhibitors are a new class of drugs for the treatment of type 2 diabetes mellitus that improve control of plasma glucose and body weight, giving great hope for the clinical utility of these agents. However, it is unclear for which patients that SGLT2 inhibitors will be useful. MATERIALS AND METHODS: We analyzed data from long-term tofogliflozin monotherapy in an open-label, randomized controlled trial in Japanese patients with type 2 diabetes mellitus...
October 15, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29032474/discrepancy-between-the-initial-assessment-of-injury-severity-and-post-hoc-determination-of-injury-severity-in-patients-with-apparently-mild-traumatic-brain-injury-a-retrospective-multicenter-cohort-analysis
#14
S M Bossers, K M Pol, E P A Oude Ophuis, B Jacobs, M C Visser, S A Loer, C Boer, J van der Naalt, P Schober
PURPOSE: Traumatic brain injury (TBI) is a major cause of trauma-related visits to emergency departments (ED). Determination of monitoring requirements of patients with apparently mild TBI is challenging. Patients may turn out to be more severely injured than initially assumed, and failure to identify these patients constitutes a serious threat to patient safety. We, therefore, aimed to identify clinical risk factors for more severe injuries in patients with apparently mild TBI. METHODS: In a retrospective cohort analysis performed at two level I trauma centers, 808 patients aged ≥ 16 presenting to the ED with head trauma and a Glasgow Coma Scale (GCS) score 13-15 who received a head CT scan were studied...
October 14, 2017: European Journal of Trauma and Emergency Surgery: Official Publication of the European Trauma Society
https://www.readbyqxmd.com/read/29032180/genomic-analysis-of-isometamidium-chloride-resistance-in-trypanosoma-congolense
#15
Eliane Tihon, Hideo Imamura, Frederik Van den Broeck, Lieve Vermeiren, Jean-Claude Dujardin, Jan Van Den Abbeele
Isometamidium Chloride (ISM) is one of the principal drugs used to counteract Trypanosoma congolense infection in livestock, both as a prophylactic as well as a curative treatment. However, numerous cases of ISM resistance have been reported in different African regions, representing a significant constraint in the battle against Animal African Trypanosomiasis. In order to identify genetic signatures associated with ISM resistance in T. congolense, the sensitive strain MSOROM7 was selected for induction of ISM resistance in a murine host...
October 6, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29031817/bcrp-abcg2-and-high-alert-medications-biochemical-pharmacokinetic-pharmacogenetic-and-clinical-implications
#16
REVIEW
Daiki Hira, Tomohiro Terada
The human breast cancer resistance protein (BCRP/ABCG2) is an ATP-binding cassette efflux transporter that uses ATP hydrolysis to expel xenobiotics from cells, including anti-cancer medications. It is expressed in the gastrointestinal tract, liver, kidney, and brain endothelium. Thus, ABCG2 functions as a tissue barrier to drug transport that strongly influences the pharmacokinetics of substrate medications. Genetic polymorphisms of ABCG2 are closely related to inter-individual variations in therapeutic performance...
October 12, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29031357/regulation-of-potassium-homeostasis-in-ckd
#17
REVIEW
Thomas D DuBose
Disturbances of potassium homeostasis can cause either hyperkalemia or hypokalemia and result in serious consequences. Although the consequences of acute and chronic hyperkalemia and treatment of these conditions in CKD have been widely appreciated by nephrologists, more recent information has focused attention on the consequences of chronic hypokalemia. Several recent studies have documented a "U-shaped" relationship between the serum [K(+)] and higher mortality in several clinical studies. The causes of dyskalemias are placed into the unique perspective of patients with CKD and its evolution with progression of CKD to later stages and focuses on the pathophysiology of these disorders...
September 2017: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/29030304/interaction-of-cruciferin-based-nanoparticles-with-caco-2-cells-and-caco-2-ht29-mtx-co-cultures
#18
Ali Akbari, Afsaneh Lavasanifar, Jianping Wu
The objective of this work was to assess the potential of Cruciferin/Calcium (Cru/Ca) and Cruciferin/Chitosan (Cru/Cs) nanoparticles for oral drug delivery. For this purpose, Cru/Ca and Cru/Cs nanoparticles were developed through cold gelation of Cruciferin, a major canola protein, and in interaction with calcium and chitosan, respectively. The extent and rate of particle uptake in Caco-2 cells and Caco-2/HT29 co-culture was then evaluated by fluorescence spectroscopy as well as flow cytometry. Through pre-incubation of Caco-2 cell monolayer with specific endocytosis inhibitors, the mechanism of cell uptake was investigated...
October 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29030288/in-vitro-characterization-of-zebrafish-danio-rerio-organic-anion-transporters-oat2a-e
#19
Jelena Dragojević, Ivan Mihaljević, Marta Popović, Roko Zaja, Tvrtko Smital
OATS/Oats are transmembrane proteins that transport a variety of drugs, environmental toxins and endogenous metabolites into the cell. Zebrafish (Danio rerio) has seven OAT orthologs: Oat1, Oat2a-e and Oat3. In this study we specifically address Oat2 (Slc22a7) family. Conserved synteny analysis showed localization of zebrafish oat2 genes on two chromosomes, 11 and 17. All five zebrafish Oats were localized by live cell imaging in membranes of transiently transfected HEK293-T cells, and Oat2a, b, d, and e were confirmed using western blot analysis...
October 10, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29030100/antimicrobial-susceptibility-profiles-of-oral-treponema-species
#20
Kazuko Okamoto-Shibayama, Jin Sekino, Kouki Yoshikawa, Atsushi Saito, Kazuyuki Ishihara
Treponemes occur in the microflora of the dental plaque. Certain Treponema species that are frequently isolated from chronic periodontitis lesions are involved in its initiation and progression. In addition to mechanical instrumentation, antimicrobial agents are used as an adjunctive treatment modality for periodontitis. Despite its importance for successful antimicrobial treatment, information about susceptibility is limited for Treponema species. The aim of this study was to assess the susceptibility of two Treponema denticola strains, Treponema socranskii, and Treponema vincentii to eleven antimicrobial agents...
October 10, 2017: Anaerobe
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