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https://www.readbyqxmd.com/read/29145252/identifications-of-potential-therapeutic-targets-and-drugs-in-angiotensin-ii-induced-hypertension
#1
Xiaoli Wu, Ruihua Fan
This study aimed to identify the underlying therapeutic targets of angiotensin II (AngII)-induced hypertension, and screen the related drugs.The gene expression profiles of GSE93579 and GSE75815 were used to identify differentially expressed genes (DEGs) between AngII-induced hypertension and control samples based on meta-analysis. These DEGs were analyzed using Gene-Ontology (GO) function and pathway enrichment methods. Subsequently, the weighed gene coexpression network analysis (WGCNA)-based meta-analysis was applied to determine transcriptional signature with DEGs...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29145171/host-target-based-approaches-against-arboviral-diseases
#2
Rebeca Froes Rocha, Juliana Lemos Del Sarto, Rafael Elias Marques, Vivian Vasconcelos Costa, Mauro Martins Teixeira
In the 20th century, socioeconomic and environmental changes facilitated the reintroduction of mosquitoes in developing cities, resulting in the reintroduction of mosquito-borne viral diseases and the dispersal of their causative agents in a worldwide scale. Recurrent outbreaks of arboviral diseases are being reported, even in regions without a previous history of arboviral disease transmission. Of note, arboviral infections represented approximately 30% of all emerging vector-borne diseases of the last decade...
November 27, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/29145150/microrna-146a-knockdown-suppresses-the-progression-of-ankylosing-spondylitis-by-targeting-dickkopf-1
#3
Guijuan Di, Lingli Kong, Qing Zhao, Tao Ding
Ankylosing spondylitis (AS) seriously threatens healthy and life quality of patients, however, there is no extremely effective drug to cure the disease. Therefore, it is urgent to understand molecular basis in the progression of AS. MicroRNA-146a (miR-146a) has been demonstrated to be associated with the development of AS. However, its molecular mechanism has not been fully established. In this study, it is found that the expression levels of miR-146a and dickkopf 1 (DKK1) were respectively upregulated and downregulated in hip capsule tissues of AS patients...
November 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29144739/protac-induced-protein-degradation-in-drug-discovery-breaking-the-rules-or-just-making-new-ones
#4
Ian Churcher
Targeted protein degradation, using bifunctional small molecules (Protacs) to remove specific proteins from within cells, has emerged as a novel drug discovery strategy with the potential to offer therapeutic interventions not achievable with existing approaches. In this perspective, the brief history of the field is surveyed from a drug discovery perspective with a focus on the key advances in knowledge which have led to the definition and exemplification of protein degradation concepts, and their resulting applications to medicine discovery...
November 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29144562/mir-5100-increases-the-cisplatin-resistance-of-the-lung-cancer-stem-cells-by-inhibiting-the-rab6
#5
Lawei Yang, Ziying Lin, Yahong Wang, Shenglan Gao, Qinglan Li, Chunyan Li, Wenya Xu, Jie Chen, Tie Liu, Zeqing Song, Gang Liu
Cisplatin-based chemotherapy is the most commonly used treatment regimen for lung cancer. Cancer stem cells (CSCs) are postulated to be important promoters of drug resistance. We previously found that miR-5100 is overexpressed in lung cancer, but it is unknown whether and how miR-5100 regulates cisplatin resistance. Here, we demonstrated that miR-5100 was significantly up-regulated in CD44 + CD133+ lung cancer stem cells (LCSCs) compared with non-CSCs. Additionally, over-expression of miR-5100 increased CSC properties, cell growth and tumor sphere formation in lung cancer cell line A549 or H1299, and that miR-5100 inhibitor significantly increased sensitivity of LCSCs to cisplatin in vitro...
November 16, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29144553/blocking-17%C3%AE-hydroxysteroid-dehydrogenase-type-1-in-endometrial-cancer-a-potential-novel-endocrine-therapeutic-approach
#6
Gonda Fj Konings, Karlijn Mc Cornel, Sofia Xanthoulea, Bert Delvoux, Margaretha A Skowron, Loes Kooreman, Pasi Koskimies, Camilla Krakstad, Helga B Salvesen, Kim van Kuijk, Yannick Jm Schrooders, Marc Vooijs, Arjan J Groot, Marlies Y Bongers, Roy Fpm Kruitwagen, Andrea Romano
The enzyme type 1 17β-hydroxysteroid dehydrogenase (17β-HSD-1), responsible for generating active 17β-estradiol (E2) from low-active estrone (E1), is over-expressed in endometrial cancer (EC) thus implicating an increased intra-tissue generation of E2 in this estrogen-dependent condition. In this study we explored the possibility of inhibiting 17β-HSD-1 and impairing the generation of E2 from E1 in EC using in vitro, in vivo and ex vivo models. We generated EC cell lines derived from the well-differentiated endometrial adenocarcinoma Ishikawa cell line and expressing levels of 17β-HSD-1 similar to human tissues...
November 16, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29144411/nucleic-acid-aptamers-emerging-applications-in-medical-imaging-nanotechnology-neurosciences-and-drug-delivery
#7
REVIEW
Pascal Röthlisberger, Cécile Gasse, Marcel Hollenstein
Recent progresses in organic chemistry and molecular biology have allowed the emergence of numerous new applications of nucleic acids that markedly deviate from their natural functions. Particularly, DNA and RNA molecules-coined aptamers-can be brought to bind to specific targets with high affinity and selectivity. While aptamers are mainly applied as biosensors, diagnostic agents, tools in proteomics and biotechnology, and as targeted therapeutics, these chemical antibodies slowly begin to be used in other fields...
November 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29144383/monitoring-for-response-to-antineoplastic-drugs-the-potential-of-a-metabolomic-approach
#8
REVIEW
Jodi Rattner, Oliver F Bathe
For most cancers, chemotherapeutic options are rapidly expanding, providing the oncologist with substantial choices. Therefore, there is a growing need to select the best systemic therapy, for any individual, that effectively halts tumor progression with minimal toxicity. Having the capability to predict benefit and to anticipate toxicity would be ideal, but remains elusive at this time. An alternative approach is an adaptive approach that involves close observation for treatment response and emergence of resistance...
November 16, 2017: Metabolites
https://www.readbyqxmd.com/read/29143960/predicting-frequent-emergency-department-use-among-children-with-epilepsy-a-retrospective-cohort-study-using-electronic-health-data-from-2-centers
#9
Zachary M Grinspan, Anup D Patel, Baria Hafeez, Erika L Abramson, Lisa M Kern
OBJECTIVE: Among children with epilepsy, to develop and evaluate a model to predict emergency department (ED) use, an indicator of poor disease control and/or poor access to care. METHODS: We used electronic health record data from 2013 to predict ED use in 2014 at 2 centers, benchmarking predictive performance against machine learning algorithms. We evaluated algorithms by calculating the expected yearly ED visits among the 5% highest risk individuals. We estimated the breakeven cost per patient per year for an intervention that reduced ED visits by 10%...
November 16, 2017: Epilepsia
https://www.readbyqxmd.com/read/29143897/anaplastic-lymphoma-kinase-testing-ihc-vs-fish-vs-ngs
#10
REVIEW
Xiaomin Niu, Jody C Chuang, Gerald J Berry, Heather A Wakelee
Personalized targeted therapy has emerged as a promising strategy in lung cancer treatment, with current attention focused on elucidation and detection of oncogenic drivers responsible for tumor initiation and maintenance and development of drug resistance. In lung cancer, several oncogenic drivers have been reported, triggering the application of tyrosine kinase inhibitors (TKIs) to target these dysfunctional genes. The anaplastic lymphoma kinase (ALK) rearrangement is responsible for about 4-7% of all non-small cell lung cancers (NSCLCs) and perhaps as high as a third in specific patient populations such as younger, male, non-smokers with advanced stage, epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) wild type, and signet ring cell adenocarcinoma with abundant intracytoplasmic mucin...
November 16, 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29143894/mechanism-of-resistance-in-gastrointestinal-stromal-tumors
#11
E Tamborini
Imatinib has revolutionized the treatment of GIST since this drug is able to inhibit tumoral growth by blocking the activity of receptor tyrosine kinases, KIT or PDGFRA, that in these tumors are constitutively activated because of the presence of mutations that alters their catalytic activity. However, despite this enormous improvement in the RFS and OS and in the quality of life of GIST patients, imatinib is not able to eradicate the disease: recurrences occur and acquired resistance is a common event which develops during targeted treatments...
November 17, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29143881/rmce-based-insect-cell-platform-to-produce-membrane-proteins-captured-on-hiv-1-gag-virus-like-particles
#12
João Vidigal, Bárbara Fernandes, Mafalda M Dias, Marco Patrone, António Roldão, Manuel J T Carrondo, Paula M Alves, Ana P Teixeira
Conformationally complex membrane proteins (MPs) are therapeutic targets in many diseases, but drug discovery has been slowed down by the lack of efficient production tools. Co-expression of MPs with matrix proteins from enveloped viruses is a promising approach to obtain correctly folded proteins at the surface of virus-like particles (VLPs), preserving their native lipidic environment. Here, we implemented a site-specific recombinase-mediated cassette exchange (RMCE) strategy to establish a reusable HIV-1 Gag-expressing insect cell line for fast production of target MPs on the surface of Gag-VLPs...
November 16, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29143818/visualization-of-chemical-modifications-in-the-human-80s-ribosome-structure
#13
S Kundhavai Natchiar, Alexander G Myasnikov, Hanna Kratzat, Isabelle Hazemann, Bruno P Klaholz
Chemical modifications of human ribosomal RNA (rRNA) are introduced during biogenesis and have been implicated in the dysregulation of protein synthesis, as is found in cancer and other diseases. However, their role in this phenomenon is unknown. Here we visualize more than 130 individual rRNA modifications in the three-dimensional structure of the human ribosome, explaining their structural and functional roles. In addition to a small number of universally conserved sites, we identify many eukaryote- or human-specific modifications and unique sites that form an extended shell in comparison to bacterial ribosomes, and which stabilize the RNA...
November 15, 2017: Nature
https://www.readbyqxmd.com/read/29143809/hypertension-promising-mitochondria-targeting-drug-for-pah
#14
Irene Fernández-Ruiz
No abstract text is available yet for this article.
November 16, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/29143777/margination-of-fluorescent-polylactic-acid-polyaspartamide-based-nanoparticles-in-microcapillaries-in-vitro-the-effect-of-hematocrit-and-pressure
#15
Emanuela Fabiola Craparo, Rosa D'Apolito, Gaetano Giammona, Gennara Cavallaro, Giovanna Tomaiuolo
The last decade has seen the emergence of vascular-targeted drug delivery systems as a promising approach for the treatment of many diseases, such as cardiovascular diseases and cancer. In this field, one of the major challenges is carrier margination propensity (i.e., particle migration from blood flow to vessel walls); indeed, binding of these particles to targeted cells and tissues is only possible if there is direct carrier-wall interaction. Here, a microfluidic system mimicking the hydrodynamic conditions of human microcirculation in vitro is used to investigate the effect of red blood cells (RBCs) on a carrier margination in relation to RBC concentration (hematocrit) and pressure drop...
October 28, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29143719/microbial-protein-targets-towards-understanding-and-intervention
#16
Paul W Denny
The rise of antimicrobial resistance, coupled with a lack of industrial focus on antimicrobial discovery over preceding decades, has brought the world to a crisis point. With both human and animal health set to decline due to increased disease burdens caused by near untreatable microbial pathogens, there is an urgent need to identify new antimicrobials. Central to this is the elucidation of new, robustly validated, drug targets. Informed by industrial practice and concerns, the use of both biological and chemical tools in validation is key...
November 16, 2017: Parasitology
https://www.readbyqxmd.com/read/29143673/the-heptestcontest-a-global-innovation-contest-to-identify-approaches-to-hepatitis-b-and-c-testing
#17
Joseph D Tucker, Kathrine Meyers, John Best, Karyn Kaplan, Razia Pendse, Kevin A Fenton, Isabelle Andrieux-Meyer, Carmen Figueroa, Pedro Goicochea, Charles Gore, Azumi Ishizaki, Giten Khwairakpam, Veronica Miller, Antons Mozalevskis, Michael Ninburg, Ponsiano Ocama, Rosanna Peeling, Nick Walsh, Massimo G Colombo, Philippa Easterbrook
BACKGROUND: Innovation contests are a novel approach to elicit good ideas and innovative practices in various areas of public health. There remains limited published literature on approaches to deliver hepatitis testing. The purpose of this innovation contest was to identify examples of different hepatitis B and C approaches to support countries in their scale-up of hepatitis testing and to supplement development of formal recommendations on service delivery in the 2017 World Health Organization hepatitis B and C testing guidelines...
November 1, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29143669/considerations-for-using-minocycline-vs-doxycycline-for-treatment-of-canine-heartworm-disease
#18
Mark G Papich
BACKGROUND: Doxycycline has been considered the first drug of choice for treating Wolbachia, a member of the Rickettsiaceae, which has a symbiotic relationship with filarial worms, including heartworms. Wolbachia, is susceptible to tetracyclines, which have been used as adjunctive treatments for heartworm disease. Treatment with doxycycline reduces Wolbachia numbers in all stages of heartworms and improves outcomes and decreased microfilaremia in dogs treated for heartworm disease. The American Heartworm Society recommends treatment with doxycycline in dogs diagnosed with heartworm disease at a dose of 10 mg/kg twice daily for 28 days...
November 9, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/29143609/survey-of-programmatic-experiences-and-challenges-in-delivery-of-hepatitis-b-and-c-testing-in-low-and-middle-income-countries
#19
Azumi Ishizaki, Julie Bouscaillou, Niklas Luhmann, Stephanie Liu, Raissa Chua, Nick Walsh, Sarah Hess, Elena Ivanova, Teri Roberts, Philippa Easterbrook
BACKGROUND: There have been few reports on programmatic experience of viral hepatitis testing and treatment in resource-limited settings. To inform the development of the 2017 World Health Organization (WHO) viral hepatitis testing guidance and in particular the feasibility of proposed recommendations, we undertook a survey across a range of organisations engaged with hepatitis testing in low- and middle-income countries (LMICs). Our objective was to describe current hepatitis B and C testing practices across a range of settings in different countries, as well as key barriers or challenges encountered and proposed solutions to promote testing scale-up...
November 1, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29143497/detection-and-monitoring-of-driver-mutations-by-next-generation-sequencing-in-squamous-cell-lung-cancer-patient-and-possible-predictive-biomarker-of-third-generation-egfr-tyrosine-kinase-inhibitors
#20
Xiaoyan Shen, Jie Shen, Hang Zhang, Yuxin Cheng, Yang Yang, Jiahui Gao, Yu Zhang, Rutian Li, Baorui Liu, Lifeng Wang
Driver mutation detection and the development of targeted drugs have significantly improved survival of advanced lung adenocarcinoma patients with driver mutations. However, we still lack understanding of druggable mutations in patients with advanced squamous cell lung cancer (SQCLC). Less than 10% of SQCLC patients have EGFR gene mutations, thus we have limited knowledge of biological molecular changes with first generation EGFR-tyrosine kinase inhibitor (TKI) resistance. We report a case of an SQCLC patient treated with first-line platinum-doublet chemotherapy...
November 16, 2017: Thoracic Cancer
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