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https://www.readbyqxmd.com/read/28448635/excited-state-dynamics-of-bis-dehydroxycurcumin-tert-butyl-ester-a-diketo-shifted-derivative-of-the-photosensitizer-curcumin
#1
Luca Nardo, Angelo Maspero, Andrea Penoni, Giovanni Palmisano, Erika Ferrari, Monica Saladini
Bis-dehydroxycurcumin tert-butyl ester (K2T23) is a derivative of the natural spice curcumin. Curcumin is widely studied for its multiple therapeutic properties, including photosensitized cytotoxicity. However, the full exploitation of curcumin phototoxic potential is hindered by the extreme instability of its excited state, caused by very efficient non radiative decay by means of transfer of the enolic proton to the nearby keto oxygen. K2T23 is designed to exhibit a tautomeric equilibrium shifted toward the diketo conformers with respect to natural curcumin...
2017: PloS One
https://www.readbyqxmd.com/read/28448002/measurement-of-t-cell-alloreactivity-using-imaging-flow-cytometry
#2
Stephen C Juvet, Sajad Moshkelgosha, Sharon Sanderson, Joanna Hester, Kathryn J Wood, Andrew Bushell
The measurement of immunological reactivity to donor antigens in transplant recipients is likely to be crucial for the successful reduction or withdrawal of immunosuppression. The mixed leukocyte reaction (MLR), limiting dilution assays, and trans-vivo delayed-type hypersensitivity (DTH) assay have all been applied to this question, but these methods have limited predictive ability and/or significant practical limitations that reduce their usefulness. Imaging flow cytometry is a technique that combines the multiparametric quantitative powers of flow cytometry with the imaging capabilities of fluorescent microscopy...
April 19, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28447740/calyptranthes-grandifolia-o-berg-myrtaceae-ethanolic-extract-inhibits-tnf-%C3%AE-gene-expression-and-cytokine-release-in%C3%A2-vitro
#3
Geórgia Muccillo Dexheimer, Luciana Knabben de Oliveira Becker Delving, Henrique Sulzbach de Oliveira, Vanderlei Biolchi, Márcia Inês Goettert, Adriane Pozzobon
Anti-tumor therapies based on anti-inflammatory effects have been considered in cancer treatment. Survival, proliferation and, resultantly, invasion and metastasis of tumor cells are regulated by local inflammatory mediators. Primary inflammatory cytokines, such as tumor necrosis factor (TNF), are targets for anticancer therapy. Several anti‑inflammatory agents isolated from natural products are becoming important chemopreventive and therapeutic agents for cancer. The present study aimed to investigate the expression of TNF‑α, nuclear factor‑κΒ (NF‑κΒ) and p38α mitogen-activated protein kinase (p38α) genes, associated with proliferation and inflammation in the Caco‑2 cell line treated with ethanolic and hexanic extracts of Calyptranthes grandifolia O...
March 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447602/spatial-computation-of-intratumoral-t-cells-correlates-with-survival-of-patients-with-pancreatic-cancer
#4
Julienne L Carstens, Pedro Correa de Sampaio, Dalu Yang, Souptik Barua, Huamin Wang, Arvind Rao, James P Allison, Valerie S LeBleu, Raghu Kalluri
The exact nature and dynamics of pancreatic ductal adenocarcinoma (PDAC) immune composition remains largely unknown. Desmoplasia is suggested to polarize PDAC immunity. Therefore, a comprehensive evaluation of the composition and distribution of desmoplastic elements and T-cell infiltration is necessary to delineate their roles. Here we develop a novel computational imaging technology for the simultaneous evaluation of eight distinct markers, allowing for spatial analysis of distinct populations within the same section...
April 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28447465/transferrin-dressed-virus-like-ternary-nanoparticles-with-aggregation-induced-emission-for-targeted-delivery-and-rapid-cytosolic-release-of-sirna
#5
Tingbin Zhang, Weisheng Guo, Chunqiu Zhang, Jing Yu, Jing Xu, Shuyi Li, Jian-Hua Tian, Paul C Wang, Jinfeng Xing, Xing-Jie Liang
Viruses have evolved to be outstandingly efficient at gene delivery, but their use as vectors is limited by safety risks. Inspired by the structure of viruses, we constructed a virus-mimicking vector (denoted as TR4@siRNA@Tf NCs) with virus-like architecture and infection properties. Composed of a hydrophilic peptide, an AIEgen and a lipophilic tail, TR4 imitates the viral capsid and endows the vector with aggregation-induced emission (AIE) properties as well as efficient siRNA compaction. The outer glycoprotein transferrin (Tf) mimics the viral envelope protein, and endows the vector with reduced cytotoxicity as well as enhanced targeting capability...
April 27, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28447330/seawater-drowning-associated-pneumonia-a-10-year-descriptive-cohort-in-intensive-care-unit
#6
Alexandre Robert, Pierre-Éric Danin, Hervé Quintard, Nicolas Degand, Nihal Martis, Denis Doyen, Céline Pulcini, Raymond Ruimy, Carole Ichai, Gilles Bernardin, Jean Dellamonica
BACKGROUND: Pneumonia is one of the major complications of drowning, but the optimal empirical antibiotic treatment is not clearly defined. Multidrug-resistant (MDR) bacteria and fungi have been identified in a recent series of freshwater drowning-associated pneumonia. However, microbial data in seawater drowning are scarce. The objective of the study is to describe the microorganisms isolated in early respiratory specimens obtained from seawater drowning-associated pneumonia and to provide their antibiotic susceptibility pattern...
December 2017: Annals of Intensive Care
https://www.readbyqxmd.com/read/28447115/human-genetics-as-a-model-for-target-validation-finding-new-therapies-for-diabetes
#7
REVIEW
Soren K Thomsen, Anna L Gloyn
Type 2 diabetes is a global epidemic with major effects on healthcare expenditure and quality of life. Currently available treatments are inadequate for the prevention of comorbidities, yet progress towards new therapies remains slow. A major barrier is the insufficiency of traditional preclinical models for predicting drug efficacy and safety. Human genetics offers a complementary model to assess causal mechanisms for target validation. Genetic perturbations are 'experiments of nature' that provide a uniquely relevant window into the long-term effects of modulating specific targets...
April 26, 2017: Diabetologia
https://www.readbyqxmd.com/read/28447025/metabolic-cooperation-and-competition-in-the-tumor-microenvironment-implications-for-therapy
#8
REVIEW
Seema Gupta, Amrita Roy, Bilikere S Dwarakanath
The tumor microenvironment (TME) is an ensemble of non-tumor cells comprising fibroblasts, cells of the immune system, and endothelial cells, besides various soluble secretory factors from all cellular components (including tumor cells). The TME forms a pro-tumorigenic cocoon around the tumor cells where reprogramming of the metabolism occurs in tumor and non-tumor cells that underlies the nature of interactions as well as competitions ensuring steady supply of nutrients and anapleoretic molecules for the tumor cells that fuels its growth even under hypoxic conditions...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28446911/the-immune-response-against-acinetobacter-baumannii-an-emerging-pathogen-in-nosocomial-infections
#9
REVIEW
María Guadalupe García-Patiño, Rodolfo García-Contreras, Paula Licona-Limón
Acinetobacter baumannii is the etiologic agent of a wide range of nosocomial infections, including pneumonia, bacteremia, and skin infections. Over the last 45 years, an alarming increase in the antibiotic resistance of this opportunistic microorganism has been reported, a situation that hinders effective treatments. In order to develop effective therapies against A. baumannii it is crucial to understand the basis of host-bacterium interactions, especially those concerning the immune response of the host...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28446340/peptide-dendrimer-lipid-conjugates-as-dna-and-sirna-transfection-reagents-role-of-charge-distribution-across-generations
#10
Marc Heitz, Albert Kwok, Gabriela A Eggimann, Florian Hollfelder, Tamis Darbre, Jean-Louis Reymond
Transfection reagents are used to deliver DNA and siRNA into cells to achieve genetic manipulations, and may ultimately enable nonviral gene therapy. Progress in transfection reagents is limited by the fact that such reagents cannot be easily optimized due to their polymeric nature and/or difficult synthesis. We have developed a new class of well-defined and easily modifiable transfection reagents in the form of peptide dendrimers. These dendrimers self-assemble with DNA or siRNA and lipofectin to form nanoparticles which efficiently enter mammalian cells and liberate their nucleic acid cargo...
April 26, 2017: Chimia
https://www.readbyqxmd.com/read/28446230/label-retention-and-stem-cell-marker-expression-in-the-developing-and-adult-prostate-identifies-basal-and-luminal-epithelial-stem-cell-subpopulations
#11
Jens Adam Ceder, Tilly Wilhelmina Aalders, Jack Antonius Schalken
BACKGROUND: Prostate cancer is the second most frequent cancer among males worldwide, and most patients with metastatic disease eventually develop therapy-resistant disease. Recent research has suggested the existence of cancer stem-like cells, and that such cells are behind the therapy resistance and progression. METHODS: Here, we have taken advantage of the relatively quiescent nature of stem cells to identify the slow-cycling label-retaining stem cell (LRC) populations of the prostate gland...
April 26, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28445940/suppression-of-allograft-rejection-by-cd8-cd122-pd-1-tregs-is-dictated-by-their-fas-ligand-initiated-killing-of-effector-t-cells-versus-fas-mediated-own-apoptosis
#12
Huazhen Liu, Yeshu Wang, Qiaohuang Zeng, Yu-Qun Zeng, Chun-Ling Liang, Feifei Qiu, Hong Nie, Zhenhua Dai
Mounting evidence has shown that naturally occurring CD8+CD122+ T cells are regulatory T cells (Tregs) that suppress both autoimmunity and alloimmunity. We have previously shown that CD8+CD122+PD-1+ Tregs not only suppress allograft rejection, but also are more potent in suppression than conventional CD4+CD25+ Tregs. However, the mechanisms underlying their suppression of alloimmunity are not well understood. In an adoptive T-cell transfer model of mice lacking lymphocytes, we found that suppression of skin allograft rejection by CD8+CD122+PD-1+ Tregs was mostly dependent on their expression of Fas ligand as either lacking Fas ligand or blocking it with antibodies largely abolished their suppression of allograft rejection mediated by transferred T cells...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445767/the-visualized-macrocycles-chemistry-and-application-of-fluorophore-tagged-cyclodextrins
#13
Gábor Benkovics, Milo Malanga, Éva Fenyvesi
Cyclodextrins are macrocyclic molecules able to form host-guest complexes due to their hydrophobic cavity. Because of their carbohydrate nature they do not absorb light in the UV-vis region (200-800nm), but they can be converted into spectroscopically active compounds via modification with a chromophore unit. Among the chromophores, the group of fluorophores can provide high sensitivity in analytical applications (chemosensing) and low detection limit in optical imaging methods (fluorescent microscopy). Fluorophore-tagged cyclodextrins therefore combine interesting spectroscopic properties with promising supramolecular features which make these conjugates widely applicable in various pharmaceutical fields...
April 23, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28445469/phylogenetic-ctdna-analysis-depicts-early-stage-lung-cancer-evolution
#14
Christopher Abbosh, Nicolai J Birkbak, Gareth A Wilson, Mariam Jamal-Hanjani, Tudor Constantin, Raheleh Salari, John Le Quesne, David A Moore, Selvaraju Veeriah, Rachel Rosenthal, Teresa Marafioti, Eser Kirkizlar, Thomas B K Watkins, Nicholas McGranahan, Sophia Ward, Luke Martinson, Joan Riley, Francesco Fraioli, Maise Al Bakir, Eva GrÖnroos, Francisco Zambrana, Raymondo Endozo, Wenya Linda Bi, Fiona M Fennessy, Nicole Sponer, Diana Johnson, Joanne Laycock, Seema Shafi, Justyna Czyzewska-Khan, Andrew Rowan, Tim Chambers, Nik Matthews, Samra Turajlic, Crispin Hiley, Siow Ming Lee, Martin D Forster, Tanya Ahmad, Mary Falzon, Elaine Borg, David Lawrence, Martin Hayward, Shyam Kolvekar, Nikolaos Panagiotopoulos, Sam M Janes, Ricky Thakrar, Asia Ahmed, Fiona Blackhall, Yvonne Summers, Dina Hafez, Ashwini Naik, Apratim Ganguly, Stephanie Kareht, Rajesh Shah, Leena Joseph, Anne Marie Quinn, Phil Crosbie, Babu Naidu, Gary Middleton, Gerald Langman, Simon Trotter, Marianne Nicolson, Hardy Remmen, Keith Kerr, Mahendran Chetty, Lesley Gomersall, Dean A Fennell, Apostolos Nakas, Sridhar Rathinam, Girija Anand, Sajid Khan, Peter Russell, Veni Ezhil, Babikir Ismail, Melanie Irvin-Sellers, Vineet Prakash, Jason F Lester, Malgorzata Kornaszewska, Richard Attanoos, Haydn Adams, Helen Davies, Dahmane Oukrif, Ayse U Akarca, John A Hartley, Helen L Lowe, Sara Lock, Natasha Iles, Harriet Bell, Yenting Ngai, Greg Elgar, Zoltan Szallasi, Roland F Schwarz, Javier Herrero, Aengus Stewart, Sergio A Quezada, Peter Van Loo, Caroline Dive, C Jimmy Lin, Matthew Rabinowitz, Hugo Jwl Aerts, Allan Hackshaw, Jacqui A Shaw, Bernhard G Zimmermann, Charles Swanton
The early detection of relapse following primary surgery for non-small cell lung cancer and the characterization of emerging subclones seeding metastatic sites might offer new therapeutic approaches to limit tumor recurrence. The potential to non-invasively track tumor evolutionary dynamics in ctDNA of early-stage lung cancer is not established. Here we conduct a tumour-specific phylogenetic approach to ctDNA profiling in the first 100 TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study participants, including one patient co-recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28445466/human-pluripotent-stem-cells-recurrently-acquire-and-expand-dominant-negative-p53-mutations
#15
Florian T Merkle, Sulagna Ghosh, Nolan Kamitaki, Jana Mitchell, Yishai Avior, Curtis Mello, Seva Kashin, Shila Mekhoubad, Dusko Ilic, Maura Charlton, Genevieve Saphier, Robert E Handsaker, Giulio Genovese, Shiran Bar, Nissim Benvenisty, Steven A McCarroll, Kevin Eggan
Human pluripotent stem cells (hPS cells) can self-renew indefinitely, making them an attractive source for regenerative therapies. This expansion potential has been linked with the acquisition of large copy number variants that provide mutated cells with a growth advantage in culture. The nature, extent and functional effects of other acquired genome sequence mutations in cultured hPS cells are not known. Here we sequence the protein-coding genes (exomes) of 140 independent human embryonic stem cell (hES cell) lines, including 26 lines prepared for potential clinical use...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28445112/tracking-the-evolution-of-non-small-cell-lung-cancer
#16
Mariam Jamal-Hanjani, Gareth A Wilson, Nicholas McGranahan, Nicolai J Birkbak, Thomas B K Watkins, Selvaraju Veeriah, Seema Shafi, Diana H Johnson, Richard Mitter, Rachel Rosenthal, Max Salm, Stuart Horswell, Mickael Escudero, Nik Matthews, Andrew Rowan, Tim Chambers, David A Moore, Samra Turajlic, Hang Xu, Siow-Ming Lee, Martin D Forster, Tanya Ahmad, Crispin T Hiley, Christopher Abbosh, Mary Falzon, Elaine Borg, Teresa Marafioti, David Lawrence, Martin Hayward, Shyam Kolvekar, Nikolaos Panagiotopoulos, Sam M Janes, Ricky Thakrar, Asia Ahmed, Fiona Blackhall, Yvonne Summers, Rajesh Shah, Leena Joseph, Anne M Quinn, Phil A Crosbie, Babu Naidu, Gary Middleton, Gerald Langman, Simon Trotter, Marianne Nicolson, Hardy Remmen, Keith Kerr, Mahendran Chetty, Lesley Gomersall, Dean A Fennell, Apostolos Nakas, Sridhar Rathinam, Girija Anand, Sajid Khan, Peter Russell, Veni Ezhil, Babikir Ismail, Melanie Irvin-Sellers, Vineet Prakash, Jason F Lester, Malgorzata Kornaszewska, Richard Attanoos, Haydn Adams, Helen Davies, Stefan Dentro, Philippe Taniere, Brendan O'Sullivan, Helen L Lowe, John A Hartley, Natasha Iles, Harriet Bell, Yenting Ngai, Jacqui A Shaw, Javier Herrero, Zoltan Szallasi, Roland F Schwarz, Aengus Stewart, Sergio A Quezada, John Le Quesne, Peter Van Loo, Caroline Dive, Allan Hackshaw, Charles Swanton
Background Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC. Methods In this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy...
April 26, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28445052/facile-preparation-of-drug-loaded-tristearin-encapsulated-superparamagnetic-iron-oxide-nanoparticles-using-coaxial-electrospray-processing
#17
Manoochehr Rasekh, Zeeshan Ahmad, Richard Barrie Michael Cross, Javier Hernández Gil, James D E T Wilton-Ely, Philip W Miller
Naturally occurring polymers are promising biocompatible materials that have many applications for emerging therapies, drug delivery systems and diagnostic agents. The handling and processing of such materials still constitutes a major challenge which can limit the full exploitation of their properties. This study explores an ambient environment processing technique: coaxial electrospray (CO-ES) to encapsulate genistein (an isoflavonoid and model drug), superparamagnetic iron oxide nanoparticles (SPIONs, 10-15 nm) and a fluorophore (BODIPY) into a layered (triglyceride tristearin shell) particulate system, with a view to constructing a theranostic agent...
April 26, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28444967/co-delivery-of-microrna-21-antisense-oligonucleotides-and-gemcitabine-using-nanomedicine-for-pancreatic-cancer-therapy
#18
Yaqing Li, Yinting Chen, Jiajia Li, Zuoquan Zhang, Chumei Huang, Guoda Lian, Kege Yang, Shaojie Chen, Ying Lin, Lingyun Wang, Kaihong Huang, Linjuan Zeng
Tumor metastasis occurs naturally in pancreatic cancer, and the efficacy of chemotherapy is usually poor. Precision medicine, combining down-regulation of target genes with chemotherapy drugs, is expected to improve the therapeutic effects. Therefore, we developed a combined therapy of microRNA-21 antisense oligonucleotides (ASO-miR-21) and Gemcitabine (Gem) using a targeted co-delivery nanoparticle (NP) carrier and investigated the synergistic inhibitory effects on pancreatic cancer cells metastasis and growth...
April 26, 2017: Cancer Science
https://www.readbyqxmd.com/read/28444290/low-density-lipoproteins-cause-atherosclerotic-cardiovascular-disease-1-evidence-from-genetic-epidemiologic-and-clinical-studies-a-consensus-statement-from-the-european-atherosclerosis-society-consensus-panel
#19
Brian A Ference, Henry N Ginsberg, Ian Graham, Kausik K Ray, Chris J Packard, Eric Bruckert, Robert A Hegele, Ronald M Krauss, Frederick J Raal, Heribert Schunkert, Gerald F Watts, Jan Borén, Sergio Fazio, Jay D Horton, Luis Masana, Stephen J Nicholls, Børge G Nordestgaard, Bart van de Sluis, Marja-Riitta Taskinen, Lale Tokgözoglu, Ulf Landmesser, Ulrich Laufs, Olov Wiklund, Jane K Stock, M John Chapman, Alberico L Catapano
Aims: To appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD). Methods and results: We assessed whether the association between LDL and ASCVD fulfils the criteria for causality by evaluating the totality of evidence from genetic studies, prospective epidemiologic cohort studies, Mendelian randomization studies, and randomized trials of LDL-lowering therapies. In clinical studies, plasma LDL burden is usually estimated by determination of plasma LDL cholesterol level (LDL-C)...
April 24, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28444098/the-cerebrospinal-fluid-in-multiple-sclerosis-far-beyond-the-bands
#20
Renan Barros Domingues, Gustavo Bruniera Peres Fernandes, Fernando Brunale Vilela de Moura Leite, Charles Peter Tilbery, Rodrigo Barbosa Thomaz, Gisele Sampaio Silva, Cristóvão Luis Pitangueira Mangueira, Carlos Augusto Senne Soares
The cerebrospinal fluid analysis has been employed for supporting multiple sclerosis diagnosis and ruling out the differential diagnoses. The most classical findings reflect the inflammatory nature of the disease, including mild pleocytosis, mild protein increase, intrathecal synthesis of immunoglobulin G, and, most typically, the presence of oligoclonal bands. In recent years, new biomarkers have emerged in the context of multiple sclerosis. The search for new biomarkers reflect the need of a better evaluation of disease activity, disease progression, and treatment efficiency...
January 2017: Einstein
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