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https://www.readbyqxmd.com/read/28333921/bioenergetics-based-modeling-of-plasmodium-falciparum-metabolism-reveals-its-essential-genes-nutritional-requirements-and-thermodynamic-bottlenecks
#1
Anush Chiappino-Pepe, Stepan Tymoshenko, Meriç Ataman, Dominique Soldati-Favre, Vassily Hatzimanikatis
Novel antimalarial therapies are urgently needed for the fight against drug-resistant parasites. The metabolism of malaria parasites in infected cells is an attractive source of drug targets but is rather complex. Computational methods can handle this complexity and allow integrative analyses of cell metabolism. In this study, we present a genome-scale metabolic model (iPfa) of the deadliest malaria parasite, Plasmodium falciparum, and its thermodynamics-based flux analysis (TFA). Using previous absolute concentration data of the intraerythrocytic parasite, we applied TFA to iPfa and predicted up to 63 essential genes and 26 essential pairs of genes...
March 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28332433/the-cost-effectiveness-of-alectinib-in-anaplastic-lymphoma-kinase-positive-alk-advanced-nsclc-previously-treated-with-crizotinib
#2
J J Carlson, W Canestaro, A Ravelo, W Wong
Introduction Anaplastic lymphoma kinase (ALK) targeting drugs provide an important option for advanced non-small cell lung cancer patients with this distinct tumor type; however, there is considerable uncertainty as to which drug provides the optimal value after crizotinib treatment. This study estimated the cost-utility of alectinib vs ceritinib from a US payer perspective. Methods A cost-utility model was developed using partition survival methods and three health states: progression-free (PF), post-progression (PP), and death...
March 23, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28330178/emergence-of-mixed-infection-of-beijing-non-beijing-strains-among-multi-drug-resistant-mycobacterium-tuberculosis-in-pakistan
#3
Samar Mustafa, Hasnain Javed, Jawairia Hashmi, Nazia Jamil, Zarfishan Tahir, Abdul Majeed Akhtar
Tuberculosis (TB) remains as one of the deadliest diseases after HIV globally with 95 % of deaths confined to low-and-middle income countries. Pakistan is fifth among the 22 high-burden TB countries with the incidence rate of 230/100,000 persons, however, studies related to prevalent Mycobacterium tuberculosis strains and their spread, drug resistance pattern and evolutionary genetics are inadequate. The present study was undertaken to highlight the circulation of M. tuberculosis strains causing drug resistant TB in our community by targeting the molecular marker IS6110 and then characterization of these strains as Beijing and Non-Beijing genotypes...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28325591/global-scanning-of-antihistamines-in-the-environment-analysis-of-occurrence-and-hazards-in-aquatic-systems
#4
Lauren A Kristofco, Bryan W Brooks
Concentration of the global population is increasingly occurring in megacities and other developing regions, where access to medicines is increasing more rapidly than waste management systems are implemented. Because freshwater and coastal systems are influenced by wastewater effluent discharges of differential quality, exposures in aquatic systems must be considered. Here, we performed a global scanning assessment of antihistamines (AHs), a common class of medicines, in surface waters and effluents. Antihistamines were identified, literature occurrence and ecotoxicology data on AHs collated, therapeutic hazard values (THVs) calculated, and environmental exposure distributions (EEDs) of AHs compared to ecotoxicity thresholds and drug specific THVs to estimate hazards in surface waters and effluents...
March 18, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28322271/mechanistic-and-structural-basis-of-bioengineered-bovine-cathelicidin-5-with-optimized-therapeutic-activity
#5
Bikash R Sahoo, Kenta Maruyama, Jyotheeswara R Edula, Takahiro Tougan, Yuxi Lin, Young-Ho Lee, Toshihiro Horii, Toshimichi Fujiwara
Peptide-drug discovery using host-defense peptides becomes promising against antibiotic-resistant pathogens and cancer cells. Here, we customized the therapeutic activity of bovine cathelicidin-5 targeting to bacteria, protozoa, and tumor cells. The membrane dependent conformational adaptability and plasticity of cathelicidin-5 is revealed by biophysical analysis and atomistic simulations over 200 μs in thymocytes, leukemia, and E. coli cell-membranes. Our understanding of energy-dependent cathelicidin-5 intrusion in heterogeneous membranes aided in designing novel loss/gain-of-function analogues...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28318279/substance-use-prevention-and-treatment-outcomes-for-emerging-adults-in-non-college-settings-a-meta-analysis
#6
Jordan P Davis, Douglas C Smith, Daniel A Briley
Emerging adults have the highest prevalence rate of alcohol and drug use and represent a large proportion of treatment admissions in the United States. Those who do not attend college experience higher rates of use and may not have similar advantages as those attending college. A systematic review included studies investigating prevention and treatment outcomes among emerging adults in non-college settings. We included studies reporting an average age between 18 and 25 conducted outside of college settings...
March 20, 2017: Psychology of Addictive Behaviors: Journal of the Society of Psychologists in Addictive Behaviors
https://www.readbyqxmd.com/read/28318251/molecular-simulation-studies-on-the-binding-selectivity-of-type-i-inhibitors-in-the-complexes-with-ros1-versus-alk
#7
Yuanxin Tian, Yonghuan Yu, Yudong Shen, Hua Wan, Shan Chang, Tingting Zhang, Shanhe Wan, Jiajie Zhang
ROS1 and ALK are promising targets of anti-cancer drugs for non small cell lung cancer. Since they have 49% amide acid sequence homology in the kinases domain and 77% identity at the ATP binding area, some ALK inhibitors also showed some significant responses for ROS1 in the clinical trial, such as the type-I binding inhibitor crizotinib and PF-06463922. As a newly therapeutic target, selective ROS1 inhibitor is relative rarely. Moreover, the molecular basis for the selectivity of ROS1 versus ALK still remains unclear...
March 20, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28315470/the-nitric-oxide-synthase-2-pathway-is-targeted-by-both-pro-and-anti-inflammatory-treatments-in-the-immature-human-intestine
#8
Emanuela Ferretti, Eric Tremblay, Marie-Pier Thibault, David Grynspan, Karolina M Burghardt, Marcos Bettolli, Corentin Babakissa, Emile Levy, Jean-François Beaulieu
BACKGROUND AND AIM: NO synthase 2 (NOS2) was recently identified as one the most overexpressed genes in intestinal samples of premature infants with necrotizing enterocolitis (NEC). NOS2 is widely implicated in the processes of epithelial cell injury/apoptosis and host immune defense but its specific role in inflammation of the immature human intestinal mucosa remains unclear. Interestingly, factors that prevent NEC such as epidermal growth factor (EGF) attenuate the inflammatory response in the mid-gestation human small intestine using serum-free organ culture while drugs that are associated with NEC occurrence such as the non-steroidal anti-inflammatory drug, indomethacin (INDO), exert multiple detrimental effects on the immature human intestine...
March 14, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28303962/identification-of-novel-chemotherapeutic-strategies-for-metastatic-uveal-melanoma
#9
Paolo Fagone, Rosario Caltabiano, Andrea Russo, Gabriella Lupo, Carmelina Daniela Anfuso, Maria Sofia Basile, Antonio Longo, Ferdinando Nicoletti, Rocco De Pasquale, Massimo Libra, Michele Reibaldi
Melanoma of the uveal tract accounts for approximately 5% of all melanomas and represents the most common primary intraocular malignancy. Despite improvements in diagnosis and more effective local therapies for primary cancer, the rate of metastatic death has not changed in the past forty years. In the present study, we made use of bioinformatics to analyze the data obtained from three public available microarray datasets on uveal melanoma in an attempt to identify novel putative chemotherapeutic options for the liver metastatic disease...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28303124/identification-and-characterization-of-mirnas-in-response-to-leishmania-donovani-infection-delineation-of-their-roles-in-macrophage-dysfunction
#10
Neeraj Tiwari, Vinod Kumar, Mallikarjuna Rao Gedda, Ashish K Singh, Vijay K Singh, Sreenivas Gannavaram, Surya P Singh, Rakesh K Singh
The outcome of Leishmania infection depends on parasite abilities to evade host immune response and its survival in hostile environment of host macrophages. Despite a wealth of gained crucial information, parasite strategies by which it dampens host macrophage functions remain poorly understood. Micro RNAs (miRNAs) are evolutionarily conserved class of endogenous 22-nucleotide small non-coding RNA gene products, described to participate in the regulation of almost every cellular process investigated so far...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28302506/xanthine-oxidase-inhibitory-activity-of-nicotino-isonicotinohydrazides-a-systematic-approach-from-in-vitro-in-silico-to-in-vivo-studies
#11
Humaira Zafar, Muhammad Hayat, Sumayya Saied, Momin Khan, Uzma Salar, Rizwana Malik, M Iqbal Choudhary, Khalid Mohammed Khan
Change in life style and eating habits has led to an increased prevalence of hyperuricemia worldwide. The role of hyperuricemia is no more restricted to gout, but it has a central role in progression of CVD, hypertension, metabolic syndrome, and arthritis. Among the different factors involved in regulation of serum uric acid, xanthine oxidase (XO) is the best pharmacological target to control the levels of serum uric acid as it catalyzes the final steps in uric acid production. In the current study, a systemic search for the inhibitors of xanthine oxidase, starting from synthesis to in vitro screening and leading to in vivo studies is presented...
February 28, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28302487/tug1-mediates-methotrexate-resistance-in-colorectal-cancer-via-mir-186-cpeb2-axis
#12
Changfeng Li, Yongjian Gao, Yongchao Li, Dayong Ding
Colorectal cancer (CRC) is a common malignancy, most of which remain unresponsive to chemotherapy. Methotrexate (MTX) is one of the earliest cytotoxic drugs and serves as an anti-metabolite and anti-folate chemotherapy for various types of cancer. However, MTX resistance prevents its clinical application in cancer therapy. Thereby, overcoming the drug resistance is an alternative strategy to maximize the efficacy of MTX therapies in clinics. Long non-coding RNAs (lncRNAs) have gained widespread attention in recent years...
March 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28299937/non-covalent-protein-and-peptide-functionalization-of-single-walled-carbon-nanotubes-for-bio-delivery-and-optical-sensing-applications
#13
Alessandra Antonucci, Justyna Kupis-Rozmyslowicz, Ardemis Boghossian
The exquisite structural and optical characteristics of single-walled carbon nanotubes (SWCNTs), combined with the tunable specificities of proteins and peptides, can be exploited to strongly benefit technologies with applications in fields ranging from biomedicine to industrial biocatalysis. The key to exploiting the synergism of these materials is designing protein/peptide-SWCNT conjugation schemes that preserve biomolecule activity while keeping the near-infrared optical and electronic properties of SWCNTs intact...
March 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28292329/glatiramer-acetate-treatment-persistence-but-not-adherence-in-multiple-sclerosis-patients-is-predicted-by-health-related-quality-of-life-and-self-efficacy-a-prospective-web-based-patient-centred-study-cair-study
#14
Peter Joseph Jongen, Wim A Lemmens, Erwin L Hoogervorst, Rogier Donders
BACKGROUND: In patients with relapsing remitting multiple sclerosis (RRMS) the persistence of and adherence to disease modifying drug (DMD) treatment is inadequate. To take individualised measures there is a need to identify patients with a high risk of non-persistence or non-adherence. As patient-related factors have a major influence on persistence and adherence, we investigated whether health-related quality of life (HRQoL) and self-efficacy could predict persistence or adherence. METHODS: In a prospective web-based patient-centred study in 203 RRMS patients, starting treatment with glatiramer acatete (GA) 20 mg subcutaneously daily, we measured physical and mental HRQoL (Multiple Sclerosis Quality of Life-54 questionnaire), functional and control self-efficacy (Multiple Sclerosis Self-Efficacy Scale), the 12-month persistence rate and, in persistent patients, the percentage of missed doses...
March 14, 2017: Health and Quality of Life Outcomes
https://www.readbyqxmd.com/read/28290700/metabolic-response-to-everolimus-in-patient-derived-triple-negative-breast-cancer-xenografts
#15
Leslie R Euceda, Deborah K Hill, Endre Stokke, Rana Hatem, Rania El Botty, Ivan Bièche, Elisabetta Marangoni, Tone F Bathen, Siver A Moestue
Patients with triple negative breast cancer (TNBC) are unresponsive to endocrine and anti-HER2 pharmacotherapy, limiting their therapeutic options to chemotherapy. TNBC is frequently associated with abnormalities in the PI3K/AKT/mTOR signaling pathway; drugs targeting this pathway are currently being evaluated in these patients. However, response is variable, partly due to heterogeneity within TNBC, conferring a need to identify biomarkers predicting response and resistance to targeted therapy. In this study, we used a metabolomics approach to assess response to the mTOR inhibitor everolimus in a panel of TNBC patient-derived xenografts (PDX) (n=103 animals)...
March 14, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28290473/phosphoproteomics-reveals-hmga1-a-ck2-substrate-as-a-drug-resistant-target-in-non-small-cell-lung-cancer
#16
Yi-Ting Wang, Szu-Hua Pan, Chia-Feng Tsai, Ting-Chun Kuo, Yuan-Ling Hsu, Hsin-Yung Yen, Wai-Kok Choong, Hsin-Yi Wu, Yen-Chen Liao, Tse-Ming Hong, Ting-Yi Sung, Pan-Chyr Yang, Yu-Ju Chen
Although EGFR tyrosine kinase inhibitors (TKIs) have demonstrated good efficacy in non-small-cell lung cancer (NSCLC) patients harboring EGFR mutations, most patients develop intrinsic and acquired resistance. We quantitatively profiled the phosphoproteome and proteome of drug-sensitive and drug-resistant NSCLC cells under gefitinib treatment. The construction of a dose-dependent responsive kinase-substrate network of 1548 phosphoproteins and 3834 proteins revealed CK2-centric modules as the dominant core network for the potential gefitinib resistance-associated proteins...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28287613/knockdown-of-long-non-coding-rna-xist-increases-blood-tumor-barrier-permeability-and-inhibits-glioma-angiogenesis-by-targeting-mir-137
#17
H Yu, Y Xue, P Wang, X Liu, J Ma, J Zheng, Z Li, Z Li, H Cai, Y Liu
Antiangiogenic therapy plays a significant role in combined glioma treatment. However, poor permeability of the blood-tumor barrier (BTB) limits the transport of chemotherapeutic agents, including antiangiogenic drugs, into tumor tissues. Long non-coding RNAs (lncRNAs) have been implicated in various diseases, especially malignant tumors. The present study found that lncRNA X-inactive-specific transcript (XIST) was upregulated in endothelial cells that were obtained in a BTB model in vitro. XIST knockdown increased BTB permeability and inhibited glioma angiogenesis...
March 13, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28287120/optimizing-non-invasive-radiofrequency-hyperthermia-treatment-for-improving-drug-delivery-in-4t1-mouse-breast-cancer-model
#18
Matthew J Ware, Martyna Krzykawska-Serda, Jason Chak-Shing Ho, Jared Newton, Sarah Suki, Justin Law, Lam Nguyen, Vazrik Keshishian, Maciej Serda, Kimberly Taylor, Steven A Curley, Stuart J Corr
Interactions of high-frequency radio waves (RF) with biological tissues are currently being investigated as a therapeutic platform for non-invasive cancer hyperthermia therapy. RF delivers thermal energy into tissues, which increases intra-tumoral drug perfusion and blood-flow. Herein, we describe an optical-based method to optimize the short-term treatment schedules of drug and hyperthermia administration in a 4T1 breast cancer model via RF, with the aim of maximizing drug localization and homogenous distribution within the tumor microenvironment...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28277671/enzyme-cleavable-polymeric-micelles-for-the-intracellular-de-livery-of-pro-apoptotic-peptides
#19
Hanna B Kern, Selvi Srinivasan, Anthony J Convertine, David Hockenbery, Oliver W Press, Patrick S Stayton
Peptides derived from the third Bcl-2 homology domain (BH3) renormalize apoptotic signaling by antagonizing pro-survival Bcl-2 family members. They serve as a model for potential peptide drugs that possess therapeutic activities but are limited by delivery barriers including short circulation half-lives and poor penetration into cells. A diblock polymeric micelle carrier for the BIM BH3 peptide was recently described that demonstrated anti-tumor activity in a B-cell lymphoma xenograft model [Berguig et al., Mol Ther, 2015]...
March 9, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28276722/non-steroidal-anti-inflammatory-drugs-and-blood-pressure-control-in-patients-treated-for-hypertension-results-from-the-swedish-primary-care-cardiovascular-database
#20
Charlotta Ljungman, Thomas Kahan, Linus Schiöler, Björn Wettermark, Kristina B Boström, Jan Hasselström, Per Hjerpe, Karin Manhem
PURPOSE: The aim of this observational cohort study was to investigate blood pressure level and the possibility to reach target blood pressure during concomitant use of NSAID in hypertensive patients. MATERIALS AND METHODS: From the Swedish primary care cardiovascular database (SPCCD) a cohort of 5463 patients (2007 to 2008) with at least one prescription of NSAID dispensed 6 months prior to the last blood pressure measurement were included. Clinical data were extracted from computerized medical records and linked to the Prescribed Drug Register...
February 13, 2017: Blood Pressure
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