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https://www.readbyqxmd.com/read/28340510/the-diverse-family-of-mmpl-transporters-in-mycobacteria-from-regulation-to-antimicrobial-developments
#1
REVIEW
Albertus Viljoen, Violaine Dubois, Fabienne Girard-Misguich, Mickael Blaise, Jean-Louis Herrmann, Laurent Kremer
Mycobacterial genomes contain large sets of loci encoding membrane proteins that belong to a family of multidrug resistance pumps designated Resistance-Nodulation-Cell Division (RND) permeases. Mycobacterial membrane protein Large (MmpL) transporters represent a subclass of RND transporters known to participate in the export of lipid components across the cell envelope. These surface-exposed lipids with unusual structures play key roles in the physiology of mycobacteria and/or can act as virulence factors and immunomodulators...
March 24, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28340506/neuromedin-u-alters-bioenergetics-and-expands-the-cancer-stem-cell-phenotype-in-her2-positive-breast-cancer
#2
Vanesa G Martinez, John Crown, Richard K Porter, Lorraine O'Driscoll
Neuromedin U (NmU) is a neuropeptide belonging to the neuromedin family. Recently, we reported a significant association between NmU and breast cancer, particularly correlating with increased aggressiveness, resistance to HER2-targeted therapies and overall significantly poorer outcome for patients, although the mechanism through which it exerts this effect remained unexplained. Investigating this, here we found that ectopic over-expression of NmU in HER2-positive breast cancer cells induced aberrant metabolism, with increased glycolysis, likely due to enhanced pyruvate dehydrogenase kinase activity...
March 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28340496/recent-developments-in-nanomedicine-for-melanoma-treatment
#3
REVIEW
Jian-Qin Tang, Xiao-Yang Hou, Chun-Sheng Yang, Ya-Xi Li, Yong Xin, Wen-Wen Guo, Zhi-Ping Wei, Yan-Qun Liu, Guan Jiang
Melanoma is a most aggressive skin cancer with limited therapeutic options and its incidence is increasing rapidly in recent years. The discovery and application of new targeted therapy agents have shown significant benefits. However, adverse side-effects and resistance to chemotherapy remain formidable challenges in the clinical treatment of malignant melanoma. Nanotherapeutics offers an important prospect of overcoming these drawbacks. The anti-tumoral applications of nanomedicine are varied, including those in chemotherapy, RNA interference, photothermal therapy, and photodynamic therapy...
March 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28340477/environmental-analysis-of-typical-antibiotic-resistant-bacteria-and-args-in-farmland-soil-chronically-fertilized-with-chicken-manure
#4
Xiang Zhao, Jinhua Wang, Lusheng Zhu, Weili Ge, Jun Wang
Antibiotics and the corresponding resistant bacteria and resistance genes (ARGs) are generally considered emerging pollutants. To assess the impacts of tetracycline (TC) and sulfonamide (SA) antibiotics that are eliminated with fecaluria as drug prototypes, farmland soil used to research long-term fertilization with chicken manure was collected at four sites in Shandong Province. In this study, the rates of bacterial drug resistance to the same antibiotic decreased with an increase in the concentration of that antibiotic, and the resistance rates to TCs were lower than those to SAs...
March 21, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28340475/irinotecan-upregulates-fibroblast-growth-factor-receptor-3-expression-in-colorectal-cancer-cells-which-mitigates-irinotecan-induced-apoptosis
#5
Zeynep N Erdem, Stefanie Schwarz, Daniel Drev, Christine Heinzle, Andrea Reti, Petra Heffeter, Xenia Hudec, Klaus Holzmann, Bettina Grasl-Kraupp, Walter Berger, Michael Grusch, Brigitte Marian
BACKGROUND: Irinotecan (IRI) is an integral part of colorectal cancer (CRC) therapy, but response rates are unsatisfactory and resistance mechanisms are still insufficiently understood. As fibroblast growth factor receptor 3 (FGFR3) mediates essential survival signals in CRC, it is a candidate gene for causing intrinsic resistance to IRI. METHODS: We have used cell line models overexpressing FGFR3 to study the receptor's impact on IRI response. For pathway blockade, a dominant-negative receptor mutant and a small molecule kinase inhibitor were employed...
March 21, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28340465/dumbbell-dna-templated-cunps-as-a-nano-fluorescent-probe-for-detection-of-enzymes-involved-in-ligase-mediated-dna-repair
#6
Taiping Qing, Xiaoxiao He, Dinggeng He, Xiaosheng Ye, Jingfang Shangguan, Jinquan Liu, Baoyin Yuan, Kemin Wang
DNA repair processes are responsible for maintaining genome stability. Ligase and polynucleotide kinase (PNK) have important roles in ligase-mediated DNA repair. The development of analytical methods to monitor these enzymes involved in DNA repair pathways is of great interest in biochemistry and biotechnology. In this work, we reported a new strategy for label-free monitoring PNK and ligase activity by using dumbbell-shaped DNA templated copper nanoparticles (CuNPs). In the presence of PNK and ligase, the dumbbell-shaped DNA probe (DP) was locked and could resist the digestion of exonucleases and then served as an efficient template for synthesizing fluorescent CuNPs...
March 21, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28340445/an-updated-meta-analysis-short-term-therapeutic-effects-of-repeated-transcranial-magnetic-stimulation-in-treating-obsessive-compulsive-disorder
#7
REVIEW
Dong-Dong Zhou, Wo Wang, Gao-Mao Wang, Da-Qi Li, Li Kuang
BACKGROUND: This study was conducted to evaluate the short-term therapeutic effects of using repeated transcranial magnetic stimulation (rTMS) to treat obsessive-compulsive disorder (OCD) and to examine potential influencing factors. METHOD: We searched the PubMed, EMBASE, CENTRAL, Wanfang, CNKI, and Sinomed databases on September 18, 2016 and reviewed the references of previous meta-analyses. Sham-controlled, randomized clinical trials using rTMS to treat OCD were included...
March 18, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28340411/synthesis-and-biological-evaluation-of-novel-chalcone-derivatives-as-a-new-class-of-microtubule-destabilizing-agents
#8
Xiaochao Huang, Rizhen Huang, Lingxue Li, Shaohua Gou, Hengshan Wang
A series of novel chalcone derivatives were designed and synthesized as potential antitumor agents. Structures of target molecules were confirmed by (1)H NMR, (13)C NMR and HR-MS, and evaluated for their in vitro anti-proliferative activities using MTT assay. Among them, compound 12k displayed potent activity against the test tumor cell lines including multidrug resistant human cancer lines, with the IC50 values ranged from 3.75 to 8.42 μM. In addition, compound 12k was found to induce apoptosis in NCI-H460 cells via the mitochondrial pathway, including an increase of the ROS level, loss of mitochondrial membrane potential, release of cytochrome c, down-regulation of Bcl-2, up-regulation of Bax, activation of caspase-9 and caspase-3, respectively...
March 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28340408/ongoing-evolution-of-pseudomonas-aeruginosa-pao1-sublines-complicates-studies-of-dna-damage-repair-and-tolerance
#9
Julia Sidorenko, Tatjana Jatsenko, Maia Kivisaar
Sublines of the major P. aeruginosa reference strain PAO1 are derivatives of the original PAO1 isolate, which are maintained in laboratories worldwide. These sublines display substantial genomic and phenotypic variation due to ongoing microevolution. Here, we examined four sublines, MPAO1, PAO1-L, PAO1-DSM and PAO1-UT, originated from different laboratories, and six DNA polymerase-deficient mutants from the P. aeruginosa MPAO1 transposon library for their employment in elucidation of DNA damage repair and tolerance mechanisms in P...
March 16, 2017: Mutation Research
https://www.readbyqxmd.com/read/28340367/insulin-resistance-is-associated-with-carotid-intima-media-thickness-in-non-diabetic-subjects-a-cross-sectional-analysis-of-the-elsa-brasil-cohort-baseline
#10
Itamar S Santos, Márcio S Bittencourt, Alessandra C Goulart, Maria Inês Schmidt, Maria de Fátima H S Diniz, Paulo A Lotufo, Isabela M Benseñor
BACKGROUND AND AIMS: Epidemiological studies have analyzed the association between carotid intima-media thickness (CIMT) and insulin resistance, glucose levels or glycated hemoglobin with mixed results. We aimed to evaluate the association between CIMT and homeostasis model assessment - insulin resistance (HOMA-IR), fasting and post-load plasma glucose and glycated hemoglobin in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline. METHODS: We included 8028 participants (aged 35-74 years) without diabetes or overt cardiovascular disease who had complete CIMT data at baseline...
March 10, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28340361/hdl-inhibits-saturated-fatty-acid-mediated-augmentation-of-innate-immune-responses-in-endothelial-cells-by-a-novel-pathway
#11
Wei-Yang Zhang, Daniel A Franco, Eric Schwartz, Karen D'Souza, Sheetal Karnick, Peter D Reaven
BACKGROUND AND AIMS: Peripheral insulin resistance is associated with several metabolic abnormalities, including elevated serum fatty acids that contribute to vascular injury and atherogenesis. Our goals were to examine whether saturated fatty acids can modify innate immune responses to subclinical concentrations of lipopolysaccharide (LPS) in endothelial cells, and to explore the underlying pathway and determine whether it is modified by high density lipoprotein (HDL) and other factors commonly altered in insulin resistance...
September 8, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/28340282/carfilzomib-induces-leukaemia-cell-apoptosis-via-inhibiting-elk1-kiaa1524-elk-1-cip2a-and-activating-pp2a-not-related-to-proteasome-inhibition
#12
Chun-Yu Liu, Feng-Shu Hsieh, Pei-Yi Chu, Wen-Chun Tsai, Chun-Teng Huang, Yuan-Bin Yu, Tzu-Ting Huang, Po-Shen Ko, Man-Hsin Hung, Wan-Lun Wang, Chung-Wai Shiau, Kuen-Feng Chen
Enhancing the tumour suppressive activity of protein phosphatase 2A (PP2A) has been suggested to be an anti-leukaemic strategy. KIAA1524 (also termed CIP2A), an oncoprotein inhibiting PP2A, is associated with disease progression in chronic myeloid leukaemia and may be prognostic in cytogenetically normal acute myeloid leukaemia. Here we demonstrated that the selective proteasome inhibitor, carfilzomib, induced apoptosis in sensitive primary leukaemia cells and in sensitive leukaemia cell lines, associated with KIAA1524 protein downregulation, increased PP2A activity and decreased p-Akt, but not with the proteasome inhibition effect of carfilzomib...
March 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28340275/mini-tomato-genotypes-resistant-to-the-silverleaf-whitefly-and-to-two-spotted-spider-mites
#13
G M Maciel, R S Almeida, J P R da Rocha, V Andaló, G R Marquez, N C Santos, R R Finzi
The mini tomato production has expanded, becoming an amazing alternative for enterprise. Despite all commercial potential, the cultivation has the occurrence of pests as main obstacle during the crop development. Nowadays, there are no researches that aimed obtaining genotypes with high acylsugar content, capable of providing a broad-spectrum resistance to pests. This study aimed the selection of mini tomato genotypes, with high acylsugar content, and checking the resistance level to the silverleaf whitefly [Bemisia tabaci (Gennadius)] and to the two-spotted spider mites (Tetranychus urticae Koch)...
March 22, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28340175/funresdb-a-web-resource-for-genotypic-susceptibility-testing-of-aspergillus-fumigatus
#14
Michael Weber, Jonas Schaer, Grit Walther, Kerstin Kaerger, Jörg Steinmann, Peter-Michael Rath, Birgit Spiess, Dieter Buchheidt, Axel Hamprecht, Oliver Kurzai
Therapy of invasive aspergillosis is becoming more difficult due to the emergence of azole resistance in Aspergillus fumigatus. A majority of resistant strains carries mutations in the CYP51A gene. Due to a lack of sensitivity of culture-based methods, molecular detection of A. fumigatus has become an important diagnostic tool. We set up the database FunResDB (www.nrz-myk.de/funresdb) to gather all available information about CYP51A-dependent azole resistance from published literature. In summary, the screening resulted in 79 CYP51A variants, which are linked to 59 nonsynonymous mutations...
March 11, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/28340159/detection-of-polish-clinical-aspergillus-fumigatus-isolates-resistant-to-triazoles
#15
Urszula Nawrot, Ewelina Kurzyk, Maiken Cavling Arendrup, Martyna Mroczynska, Katarzyna Wlodarczyk, Beata Sulik-Tyszka, Marta Wróblewska, Marek Ussowicz, Przemyslaw Zdziarski, Kinga Niewinska, Anna Brillowska-Dabrowska
We studied the presence of triazole resistance of 121 Aspergillus fumigatus clinical isolates collected in two Polish cities, Warsaw and Wrocław, to determine if resistance is emerging in our country. We identified five itraconazole resistant isolates (4.13%) carrying the TR34/L98H alteration in Cyp51A gene, four of which were cross-resistant to posaconazole and one to voriconazole. One isolate was intermediate susceptible to itraconazole and harbored no Cyp51A alterations. The study confirms the presence of azole resistant A...
March 4, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/28340122/potential-role-of-patients-cyp3a-status-in-clozapine-pharmacokinetics
#16
Katalin Tóth, Gábor Csukly, Dávid Sirok, Ales Belic, Ádám Kiss, Edit Háfra, Máté Déri, Ádám Menus, István Bitter, Katalin Monostory
Background: The atypical antipsychotic clozapine is effective in treatment-resistant schizophrenia; however, the success or failure of clozapine therapy is substantially affected by the variables that impact the clozapine blood concentration. Thus, elucidating the inter-individual differences in clozapine pharmacokinetics can facilitate the personalized therapy. Methods: Since potential role in clozapine metabolism is assigned to CYP1A2, CYP2C19, CYP2D6 and CYP3A enzymes, the association between the patients' CYP-status (CYP genotypes, CYP expression) and clozapine clearance was evaluated in 92 psychiatric patients...
March 18, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28340105/morin-stain-detects-aluminum-containing-macrophages-in-macrophagic-myofasciitis-and-vaccination-granuloma-with-high-sensitivity-and-specificity
#17
Rati Chkheidze, Dennis K Burns, Charles L White, Diana Castro, Julie Fuller, Chunyu Cai
Macrophagic myofasciitis (MMF) is an inflammatory condition associated with the intramuscular (i.m.) injection of aluminum adjuvant-containing vaccines. It is clinically characterized by myalgia, weakness, and chronic fatigue and histologically by aggregates of cohesive macrophages with abundant basophilic, periodic acid-Schiff (PAS)-positive, diastase-resistant granules that percolate through the peri- and endomysium without eliciting substantial myofiber damage. The definitive diagnosis of MMF requires demonstration of aluminum within these macrophages...
March 15, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28340087/nutrigenomic-point-of-view-on-effects-and-mechanisms-of-action-of-ruminant-trans-fatty-acids-on-insulin-resistance-and-type-2-diabetes
#18
Bénédicte L Tremblay, Iwona Rudkowska
Evidence from observational studies suggests beneficial effects of ruminant trans fatty acids (rTFA) on insulin resistance (IR) and type 2 diabetes (T2D). However, beneficial effects of rTFA are not always observed in cell, animal, and human studies. This narrative review presents potential mechanisms of action of rTFA using nutrigenomics and microRNA results in an integrative model. In addition, the review presents factors, including measures of IR and T2D, dose and duration of studies, as well as health status, ethnicity, and genotypes of subjects, that may help explain the heterogeneity in response to rTFA supplementation...
March 7, 2017: Nutrition Reviews
https://www.readbyqxmd.com/read/28340057/long-term-outcome-of-pulmonary-vein-isolation-in-patients-with-paroxysmal-atrial-fibrillation-and-brugada-syndrome
#19
Giacomo Mugnai, Burak Hünük, Erwin Ströker, Diego Ruggiero, Hugo Enrique Coutino-Moreno, Ken Takarada, Valentina De Regibus, Rajin Choudhury, Juan Pablo Abugattas de Torres, Darragh Moran, Saverio Iacopino, Pasquale Filannino, Giulio Conte, Juan Sieira, Jan Poelaert, Stefan Beckers, Pedro Brugada, Carlo de Asmundis, Gian-Battista Chierchia
Aims: The therapeutical management of atrial fibrillation (AF) in the setting of Brugada syndrome (BS) might be challenging as many antiarrhythmic drugs (AADs) with sodium channel blocking properties might lead to to the development of ventricular arrhythmias. This study sought to evaluate the clinical outcome in a consecutive series of patients with BS having undergone pulmonary vein (PV) isolation by means of radiofrequency (RF) or cryoballoon (CB) ablation and the efficacy of catheter ablation for preventing inappropriate interventions delivered by implantable cardioverter defibrillators (ICD) on a 3-year follow up...
March 9, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28339967/placental-transporter-localization-and-expression-in-the-human-the-importance-of-species-sex-and-gestational-age-differences1
#20
Natasha Walker, Panagiotis Filis, Ugo Soffientini, Michelle Bellingham, Peter J O'Shaughnessy, Paul A Fowler
The placenta is a critical organ during pregnancy, essential for the provision of an optimal intrauterine environment, with fetal survival, growth and development relying on correct placental function. It must allow nutritional compounds and relevant hormones to pass into the fetal bloodstream and metabolic waste products to be cleared. It also acts as a semi-permeable barrier to potentially harmful chemicals both endogenous and exogenous. Transporter proteins allow for bidirectional transport and are found in the syncytiotrophoblast of the placenta and endothelium of fetal capillaries...
March 7, 2017: Biology of Reproduction
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