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https://www.readbyqxmd.com/read/28930981/generation-of-prostate-cancer-cell-models-of-resistance-to-the-anti-mitotic-agent-docetaxel
#1
Lisa Mohr, Marc Carceles-Cordon, Jungreem Woo, Carlos Cordon-Cardo, Josep Domingo-Domenech, Veronica Rodriguez-Bravo
Microtubule targeting agents (MTAs) are a mainstay in the treatment of a wide range of tumors. However, acquired resistance to chemotherapeutic drugs is a common mechanism of disease progression and a prognostic-determinant feature of malignant tumors. In prostate cancer (PC), resistance to MTAs such as the taxane Docetaxel dictates treatment failure as well as progression towards lethal stages of disease that are defined by a poor prognosis and high mortality rates. Though studied for decades, the array of mechanisms contributing to acquired resistance are not completely understood, and thus pose a significant limitation to the development of new therapeutic strategies that could benefit patients in these advanced stages of disease...
September 8, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28930531/isolongifolene-attenuates-rotenone-induced-mitochondrial-dysfunction-oxidative-stress-and-apoptosis
#2
Rengasamy Balakrishnan, Namasivayam Elangovan, Thangavel Mohankumar, Jegadeesan Nataraj, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Musthafa Mohamed Essa, Mohammed Akbar, Mohammed Abdul Sattar Khan
The present study was carried out to investigate the neuroprotective effects of isolongifolene (ILF), a tricyclic sesquiterpene of Murraya koenigii, against rotenone-induced mitochondrial dysfunction, oxidative stress and apoptosis in a cellular model. SH-SY5Y human neuroblastoma cells were divided into four experimental groups (control, rotenone (100 nM), ILF (10 microM) + rotenone (100 nanoM), ILF 10 microM alone treated) based on 3-(4, 5-dimethyl 2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The results of the present study showed that the ILF treatment significantly alleviated rotenone-induced cytotoxicity, oxidative stress and mitochondrial dysfunction in SH-SY5Y cells...
January 1, 2018: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/28927898/developmental-toxicity-assessment-of-common-excipients-using-a-stem-cell-based-in-vitro-morphogenesis-model
#3
Chloe J Yuan, Yusuke Marikawa
Various chemical compounds can inflict developmental toxicity when sufficiently high concentrations are exposed to embryos at the critical stages of development. Excipients, such as coloring agents and preservatives, are pharmacologically inactive ingredients that are included in various medications, foods, and cosmetics. However, concentrations that may adversely affect embryo development are largely unknown for most excipients. Here, the lowest observed adverse effect level (LOAEL) to inflict developmental toxicity was assessed for three coloring agents (allura red, brilliant blue, and tartrazine) and three preservatives (butylated hydroxyanisole, metabisulfite, and methylparaben)...
September 16, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28927812/bi-pssm-position-specific-scoring-matrix-based-intelligent-computational-model-for-identification-of-mycobacterial-membrane-proteins
#4
Muslim Khan, Maqsood Hayat, Sher Afzal Khan, Saeed Ahmad, Nadeem Iqbal
Mycobacterium is a pathogenic bacterium, which is a causative agent of tuberculosis (TB) and leprosy. These diseases are very crucial and become the cause of death of millions of people every year in the world. So, the characterize structure of membrane proteins of the protozoan play a vital role in the field of drug discovery because, without any knowledge about this Mycobacterium's membrane protein and their types, the scientists are unable to treat this pathogenic protozoan. So, an accurate and competitive computational model is needed to characterize this uncharacterized structure of mycobacterium...
September 16, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28927529/targeting-telomerase-and-telomeres-to-enhance-ionizing-radiation-effects-in-in-vitro-and-in-vivo-cancer-models
#5
REVIEW
F Berardinelli, E Coluzzi, A Sgura, A Antoccia
One of the hallmarks of cancer consists in the ability of tumor cells to divide indefinitely, and to maintain stable telomere lengths throughout the activation of specific telomere maintenance mechanisms (TMM). Therefore in the last fifteen years, researchers proposed to target telomerase or telomeric structure in order to block limitless replicative potential of cancer cells providing a fascinating strategy for a broad-spectrum cancer therapy. In the present review, we report in vitro and in vivo evidence regarding the use of chemical agents targeting both telomerase or telomere structure and showing promising antitumor effects when used in combination with ionizing radiation (IR)...
July 2017: Mutation Research
https://www.readbyqxmd.com/read/28926374/reducing-urban-violence-a-contrast-of-public-health-and-criminal-justice-approaches
#6
Magdalena Cerdá, Melissa Tracy, Katherine M Keyes
BACKGROUND: Cities are investing millions in Cure Violence, a public health approach to reduce urban violence by targeting at-risk youth and redirecting conflict to non-violent responses. The impact of such a program compared to criminal justice responses is unknown because experiments directly comparing criminal justice and public health approaches to violence prevention are infeasible with observational data. We simulated experiments to test the influence of two interventions on violence: a) Cure Violence; and b) directed police patrol in violence hot spots...
September 18, 2017: Epidemiology
https://www.readbyqxmd.com/read/28926192/testing-of-a-bioactive-moldable-bone-graft-substitute-in-an-infected-critically-sized-segmental-defect-model
#7
Matt E Brown, Yuan Zou, Rebecca Peyyala, Sarandeep S Huja, Larry L Cunningham, Todd A Milbrandt, Thomas D Dziubla, David A Puleo
Large infected bone defects, often resulting from high energy traumas, are difficult to treat due to their variability in complexity and location. Standard treatment for infected bone defects begins with a protocol that includes a series of debridements in conjunction with an extended course of systemic antibiotics. Only after the infection has been eliminated will repair of the defect commence, typically with implantation of autologous bone. To address some of the shortcomings of the standard treatment methods, such as serial procedures, limited grafting material, and the need for a second surgical site for autologous bone, a sequential, dual drug-releasing, moldable, calcium sulfate-based bone graft substitute was developed previously...
September 19, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28926128/copper-catalysed-aminoboration-of-vinylarenes-with-hydroxylamine-esters-a-computational-mechanistic-study
#8
Sven Tobisch
This first comprehensive computational study of the copper-mediated formal aminoboration utilising an electrophilic strategy has identified the most accessible pathway for the productive catalysis. The mechanistic picture derived from smooth energy profiles acquired by employing a reliable computational protocol applied to a realistic catalyst model conforms to all available experimental data. The high degree of chemo- and stereoselectivity achieved in syn-borylcupration and Umpolung electrophilic amination is instrumental to the exclusive generation of the (syn)-beta-aminoalkylborane product...
September 19, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28925878/genistein-induces-alterations-of-epigenetic-modulatory-signatures-in-human-cervical-cancer-cells
#9
Madhumitha Kedhari Sundaram, Mohammad Zeeshan Ansari, Abdullah Al Mutery, Maryam Ashraf, Reem Nasab, Sheethal Rai, Naushad Rais, Arif Hussain
Introduction Epidemiological studies indicate that diet rich in fruits and vegetables are associated with decreased cancer risk thereby indicating that dietary polyphenols can be potential chemo-preventive agents. The reversible nature of epigenetic modifications makes them a favorable target for cancer prevention. Polyphenols have been shown to reverse aberrant epigenetic patterns by targeting the regulatory enzymes, DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). In vitro and in silico studies of DNMTs and HDACs were planned to examine genistein's role as a natural epigenetic modifier in human cervical cancer cells, HeLa...
September 18, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28924210/kinase-inhibitor-screening-using-artificial-neural-networks-and-engineered-cardiac-biowires
#10
Genevieve Conant, Samad Ahadian, Yimu Zhao, Milica Radisic
Kinase inhibitors are often used as cancer targeting agents for their ability to prevent the activation of cell growth and proliferation signals. Cardiotoxic effects have been identified for some marketed kinase inhibitors that were not detected during clinical trials. We hypothesize that more predictive cardiac functional assessments of kinase inhibitors on human myocardium can be established by combining a high-throughput two-dimensional (2D) screening assay and a high-content three-dimensional (3D) engineered cardiac tissue (Biowire(TM)) based assay, and using human induced pluripotent stem cell-derived CMs (hiPSC-CMs)...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28922720/1-25-oh-2d3-deficiency-increases-tm40d-tumor-growth-in-bone-and-accelerates-tumor-induced-bone-destruction-in-a-breast-cancer-bone-metastasis-model
#11
Guangping Lu, Jun Li, Jiahui Chu, Shidai Jin, Ziyi Fu, Dengshun Miao, Yongmei Yin
Breast cancer is one of the most common malignancies and bone is the commonest site of distant metastases. Evidences indicate that adequate supply of vitamin D will decrease the morbidity and mortality of breast cancer. However, the main role of vitamin D deficiency in breast cancer bone metastases remains unclear. In this study, the relationship between vitamin D and breast cancer bone metastases were evaluated. Results showed that 1,25(OH)2D3 can not only inhibit the proliferation, migration and invasion of breast cancer cell TM40D in vitro, but also attenuate the breast cancer cell TM40D-induced bone destruction in vivo, whose underlying mechanism was at least partially through decreasing the number of the osteoclasts...
September 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28922613/the-etiology-of-community-acquired-pneumonia-among-children-under-5%C3%A2-years-of-age-in-mainland-china-2001-2015-a-systematic-review
#12
Guijun Ning, Xuxia Wang, Dan Wu, Zundong Yin, Yixing Li, Huaqing Wang, Weizhong Yang
BACKGROUND: The aim of this systematic review was to examine the etiology of community-acquired pneumonia (CAP) among Chinese children younger than 5 years and provide evidence for further cost-effectiveness analyses for vaccine development, diagnostic strategies and empirical treatments. METHODS: The literature review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data were obtained by searching PubMed, Embase, Web-of Science, and the Chinese databases Wanfang Data and China National Knowledge Infrastructure...
September 18, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28922513/purpose-processes-partnerships-and-products-4ps-to-advance-participatory-socio-environmental-modeling
#13
Steven Gray, Alexey Voinov, Michael Paolisso, Rebecca Jordan, Todd BenDor, Pierre Bommel, Pierre Glynn, Beatrice Hedelin, Klaus Hubacek, Josh Introne, Nagesh Kolagani, Bethany Laursen, Christina Prell, Laura Schmitt-Olabisi, Alison Singer, Eleanor Sterling, Moira Zellner
Including stakeholders in environmental model building and analysis is an increasingly popular approach to understanding ecological change. This is because stakeholders often hold valuable knowledge about socio-environmental dynamics and collaborative forms of modeling produce important boundary objects used to collectively reason about environmental problems. Although the number of participatory modeling (PM) case studies and the number of researchers adopting these approaches has grown in recent years, the lack of standardized reporting and limited reproducibility have prevented PM's establishment and advancement as a cohesive field of study...
September 18, 2017: Ecological Applications: a Publication of the Ecological Society of America
https://www.readbyqxmd.com/read/28921642/clinical-pharmacology-tools-and-evaluations-to-facilitate-comprehensive-dose-finding-in-oncology-a-continuous-risk-benefit-approach
#14
Julie M Bullock, Tiffany Lin, Sanela Bilic
Targeted therapies are now considered an integral component in the treatment armamentarium for many malignancies, and the approach to developing these drugs needs to be refined from the previous cytotoxic paradigm of toxicity-guided dose finding and identification of maximum tolerated dose to a paradigm driven by target activity. Moving away from the toxicity-driven dose finding and justification model requires an integrated approach in order to adequately characterize the risk-benefit of a drug. This approach starts with understanding the importance of collecting samples for pharmacokinetic and pharmacodynamic assessments in all phases of clinical development to fully characterize the pharmacokinetics and identify covariates and then correlating exposure to key markers of safety and efficacy in pharmacometric analyses to perform a robust risk-benefit assessment and establish the right dose...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921512/dacomitinib-induced-diarrhea-targeting-chloride-secretion-with-crofelemer
#15
Ysabella Z A Van Sebille, Rachel J Gibson, Hannah R Wardill, Imogen A Ball, Dorothy M K Keefe, Joanne M Bowen
Dacomitinib, an irreversible small-molecule pan-ErbB TKI, has a high incidence of diarrhea which has been suggested to be due to chloride secretory mechanisms. Based on this hypothesis, crofelemer, an anti-secretory agent may be an effective intervention. T84 monolayers were treated with 1µM dacomitinib and 10µM crofelemer, and mounted into Ussing chambers for electrogenic ion analysis. Crofelemer attenuated increases in chloride secretion in cells treated with dacomitinib. Albino Wistar rats (n=48) were treated with 7...
September 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28920518/the-indirect-costs-of-underfunding-foreign-partners-in-global-health-research-a-case-study
#16
Johanna T Crane, Irene Andia Biraro, Tamer M Fouad, Yap Boum, David R Bangsberg
This study of a global health research partnership assesses how U.S. fiscal administrative policies impact capacity building at foreign partner institutions. We conducted a case study of a research collaboration between Mbarara University of Science and Technology (MUST) in Mbarara, Uganda, and originally the University of California San Francisco (UCSF), but now Massachusetts General Hospital (MGH). Our case study is based on three of the authors' experiences directing and working with this partnership from its inception in 2003 through 2015...
September 16, 2017: Global Public Health
https://www.readbyqxmd.com/read/28919026/a-novel-fap%C3%AE-based-z-gly-pro-epirubicin-prodrug-for-improving-tumor-targeting-chemotherapy
#17
Jun Wang, Qiuwen Li, Xiaojuan Li, Weiqi Yuan, Sichao Huang, Shaohui Cai, Jun Xu
Fibroblast activation protein-α (FAPα) is a serine protease of the post-prolyl peptidase family that is specifically expressed in the majority of human epithelial tumors, but not in normal tissues. In this study, we demonstrated the anti-tumor activity of a novel targeting drug formed by conjugating epirubicin (EPI) with an FAPα-specific dipeptide (Z-Gly-Pro) and named it Z-GP-EPI. Consistent with this tumor-targeting delivery strategy, the results illustrated that Z-GP-EPI could release EPI efficiently after incubating with FAPα and could exhibit similar antitumor effects as EPI in vitro in FAPα over-expressed tumor cells (4T1/FAPα(+))...
September 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28918462/development-of-a-new-scoring-system-to-predict-5-year-incident-diabetes-risk-in-middle-aged-and-older-chinese
#18
Xu Han, Jing Wang, Yaru Li, Hua Hu, Xiulou Li, Jing Yuan, Ping Yao, Xiaoping Miao, Sheng Wei, Youjie Wang, Yuan Liang, Xiaomin Zhang, Huan Guo, An Pan, Handong Yang, Tangchun Wu, Meian He
AIMS: The aim of this study was to develop a new risk score system to predict 5-year incident diabetes risk among middle-aged and older Chinese population. METHODS: This prospective study included 17,690 individuals derived from the Dongfeng-Tongji cohort. Participants were recruited in 2008 and were followed until October 2013. Incident diabetes was defined as self-reported clinician diagnosed diabetes, fasting glucose ≥7.0 mmol/l, or the use of insulin or oral hypoglycemic agent...
September 16, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28917929/development-of-carboxymethyl-cellulose-chitosan-hybrid-micro-and-macroparticles-for-encapsulation-of-probiotic-bacteria
#19
P Singh, B Medronho, L Alves, G J da Silva, M G Miguel, B Lindman
Novel carboxymethyl cellulose-chitosan (CMC-Cht) hybrid micro- and macroparticles were successfully prepared in aqueous media either by drop-wise addition or via nozzle-spray methods. The systems were either physically or chemically crosslinked using genipin as the reticulation agent. The macroparticles (ca. 2mm) formed are found to be essentially of the core-shell type, while the microparticles (ca. 5μm) are apparently homogeneous. The crosslinked particles are robust, thermally resistant and less sensitive to pH changes...
November 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28917782/studies-on-the-retention-mechanism-of-solutes-in-hydrophilic-interaction-chromatography-using-stoichiometric-displacement-theory-i-the-linear-relationship-of-lgk-vs-lg-h2o
#20
Fei Wang, Fan Yang, Yang Tian, Jiawei Liu, Jiwei Shen, Quan Bai
A stoichiometric displacement model for retention (SDM-R) of small solutes and proteins based on hydrophilic interaction chromatography (HILIC) was presented. A linear equation that related the logarithm of the capacity factor of the solute to the logarithm of the concentration of water in the mobile phase was derived. The stoichiometric displacement parameters, Z (the number of water molecules required to displace a solute from ligands) and lgI (containing a number of constants that relate to the affinity of solute to the ligands) could be obtained from the slope and the intercept of the linear plots of lgk' vs...
January 1, 2018: Talanta
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