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https://www.readbyqxmd.com/read/27921229/an-extracellular-proteasome-releases-endostatin-from-human-collagen-xviii
#1
Maria L V Reiss-Pistilli, Detlef Schuppan, Madalena M S Barroso, Iranaia Assunção-Miranda, Shirley Farias, Letícia Lery, Michael Bauer, Luiz Juliano, Maria A Juliano, Tatiana Coelho-Sampaio
Endostatin is a potent anti-angiogenic and anti-tumor protein capable of regressing tumors without inducing acquired resistance. Since it is a fragment of the parental molecule, collagen XVIII, its endogenous production depends on the activity of a specific proteolytic enzyme. While such an enzyme has been described in mice, a human counterpart has not been identified so far. Here, we searched for this enzyme by using a fluorescence resonance energy transfer peptide containing the cleavage site of human collagen XVIII...
December 5, 2016: Angiogenesis
https://www.readbyqxmd.com/read/27920500/design-synthesis-and-evaluation-of-vegf-sirna-crs-as-a-novel-vector-for-gene-delivery
#2
Wen Zhao, Yifan Zhang, Xueyun Jiang, Chunying Cui
Small interfering RNA (siRNA) delivery is a prospective method in gene therapy, but it has application limitations such as negative charge, water solubility and high molecular weight. In this study, a safe and efficient nano-vector, CRS, was designed and synthesized to facilitate siRNA delivery. Physical and chemical properties of VEGF-siRNA/CRS were characterized by methods including scanning electron microscopy (SEM), transmission electron microscopy, zeta potential (ζ) measurement, drug-releasing rate measurement, gel electrophoresis and confocal microscopy...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27920467/possible-therapeutic-role-of-ige-blockade-in-irritable-bowel-syndrome
#3
EDITORIAL
Eli Magen, Tinatin Chikovani
Omalizumab is a humanized monoclonal antibody that binds to the high-affinity type-I IgE Fc receptors on mast cells (MCs) and basophils, inhibiting the IgE immune pathway. Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder, and dysregulation of the immune system likely contributes to its etiology and/or symptomatology. Colonic biopsies from patients with IBS demonstrate considerable increase in the number of degranulating MCs releasing histamine in proximity to nerves, and this event may underlie the common IBS symptom of abdominal pain...
November 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27919896/cephalosporin-3-diazeniumdiolate-no-donor-prodrug-pyrro-c3d-enhances-azithromycin-susceptibility-of-non-typeable-haemophilus-influenzae-biofilms
#4
Samuel A Collins, Michael J Kelso, Ardeshir Rineh, Nageshwar R Yepuri, Janice Coles, Claire L Jackson, Georgia D Halladay, Woolf T Walker, Jeremy S Webb, Luanne Hall-Stoodley, Gary J Connett, Martin Feelisch, Saul N Faust, Jane S A Lucas, Raymond N Allan
OBJECTIVES: PYRRO-C3D is a cephalosporin-3-diazeniumdiolate nitric oxide (NO)-donor prodrug designed to selectively deliver NO to bacterial infection sites. The objective of this study was to assess the activity of PYRRO-C3D against non-typeable Haemophilus influenzae (NTHi) biofilms and examine the role of NO in reducing biofilm-associated antibiotic tolerance. METHODS: The activity of PYRRO-C3D on in vitro NTHi biofilms was assessed through CFU enumeration and confocal microscopy...
December 5, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27917413/efficacy-of-s-lacosamide-in-preclinical-models-of-cephalic-pain
#5
Aubin Moutal, Nathan Eyde, Edwin Telemi, Ki Duk Park, Jennifer Y Xie, David W Dodick, Frank Porreca, Rajesh Khanna
Migraine is one of the world's most common neurological disorders. Current acute migraine treatments have sub-optimal efficacy and new therapeutic options are needed. Approaches targeting calcitonin gene related peptide (CGRP) signaling are clinically effective but small molecule antagonists have not been advanced due to toxicity. In this study, we explored the axonal growth/specification collapsin response mediator protein 2 (CRMP2) as a novel "druggable" target for inhibiting CGRP release and for potential relevance for treatment of migraine pain...
June 2016: Pain Reports (Baltimore, Md.)
https://www.readbyqxmd.com/read/27916642/magnetic-hyperthermia-and-ph-responsive-effective-drug-delivery-to-the-sub-cellular-level-of-human-breast-cancer-cells-by-modified-cofe2o4-nanoparticles
#6
Yunok Oh, Madhappan Santha Moorthy, Panchanathan Manivasagan, Subramaniyan Bharathiraja, Junghwan Oh
Magnetic iron oxide nanoparticles (MNPs) have been extensively utilized in a wide range of biomedical applications including magnetic hyperthermia agent. To improve the efficiency of the MNPs in therapeutic applications, in this study, we have synthesized CoFe2O4 nanoparticles and its surface was further functionalized with meso-2,3-dimercaptosuccinic acid (DMSA). The anticancer agent, Doxorubucin (DOX) was conjugated with CoFe2O4@DMSA nanoparticle to evaluate the combined effects of thermotherapy and chemotherapy...
December 1, 2016: Biochimie
https://www.readbyqxmd.com/read/27915030/the-effect-of-anionic-dicephalic-surfactants-on-fabrication-of-varied-core-nanocarriers-for-sustained-release-of-porphyrin-photosensitizers
#7
Urszula Bazylińska, Renata Frąckowiak, Zbigniew Brzózka, Kazimiera A Wilk
Double-headed anionic surfactants could provide a profound group of efficient stabilizers of new template-mediated nanocarriers for effective encapsulation and sustained release of highly hydrophobic photosensitizers, and therefore their improved therapeutic activity in photodynamic therapy (PDT) protocols. We have thus encapsulated porphyrin-origin dyes, i.e., verteporfin (VP) and meso-tetraphenylporphyrin (TPP) in different types of sodium alkyliminobisacetates, Cn(COONa)2-stabilized nanosystems including biocompatible poly(l-glutamic acid)/poly(l-lysine) - PGA/PLL, multilayer nanocapsules (NCs)...
November 19, 2016: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/27913530/cytokine-release-syndrome-with-novel-therapeutics-for-acute-lymphoblastic-leukemia
#8
Noelle V Frey, David L Porter
T-cell-engaging immunotherapies are exciting new approaches to treat patients with acute lymphoblastic leukemia (ALL). These unique agents, which include blinatumomab, a CD3/CD19 bispecific antibody, and chimeric antigen receptor (CAR) modified T cells targeted to CD19 have shown unprecedented remission rates in the relapsed, refractory ALL setting. Cytokine release syndrome (CRS), resulting from the high magnitude of immune activation by these therapies, is the most significant treatment-related toxicity. CRS manifests with fever and malaise and can progress to life-threatening capillary leak with hypoxia and hypotension...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913525/checkpoint-inhibition-in-myeloma
#9
Don M Benson
Historically, attempts at cancer immunotherapy have emphasized strategies designed to stimulate or augment the immune system into action. In the past decade, a complementary approach has developed, that of releasing immune cells from inhibitory restraint. Discoveries in the fundamental biology of how immunity is regulated, how the immune system interfaces with malignancy, and how cancer cells may exploit these processes to evade detection have all been translated into the rapidly growing field of therapeutic immune checkpoint inhibition for cancer...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913127/co-assembly-of-doxorubicin-and-curcumin-targeted-micelles-for-synergistic-delivery-and-improving-anti-tumor-efficacy
#10
Wenzhuan Ma, Qiang Guo, Ying Li, Xiaohui Wang, Jinling Wang, Pengfei Tu
Chemotherapeutic drugs have a series of limitations in anti-tumor treatment, mainly including multidrug resistance (MDR) and serious adverse reactions. Co-delivery system with two or more synergistic therapeutic drugs is an effective strategy to settle these limitations. In this study, active tumor-targeted co-delivery micelles (DOX+Cur)-PMs, with two synergistic drugs of a therapeutic drug of doxorubicin (DOX) and a chemosensitizer of curcumin (Cur) co-encapsulated into hyaluronic acid-vitamin E succinate (HA-VES) graft copolymer, were prepared and delivered simultaneously into tumor cells for improving therapeutic effects of DOX...
November 29, 2016: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/27912071/classical-and-alternative-macrophages-have-impaired-function-during-acute-and-chronic-hiv-1-infection
#11
Leonardo J Galvão-Lima, Milena S Espíndola, Luana S Soares, Fabiana A Zambuzi, Maira Cacemiro, Caroline Fontanari, Valdes R Bollela, Fabiani G Frantz
OBJECTIVES: Three decades after HIV recognition and its association with AIDS development, many advances have emerged - especially related to prevention and treatment. Undoubtedly, the development of Highly Active Antiretroviral Therapy (HAART) dramatically changed the future of the syndrome that we know today. In the present study, we evaluate the impact of HAART on macrophage function and its relevance to HIV pathogenesis. METHODS: PBMCs were isolated from blood samples and monocytes (CD14+ cells) were purified...
November 29, 2016: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27911406/ultrasound-guided-botulinum-toxin-a-injections-a-method-of-treating-sialorrhea
#12
Pierangelo Barbero, Marco Busso, Carlo Alberto Artusi, Stefania De Mercanti, Marco Tinivella, Andrea Veltri, Luca Durelli, Marinella Clerico
Neurological diseases can be complicated by sialorrhea, an excessive flow of saliva. Patients suffering from moderate to severe sialorrhea have an impaired quality of life, often worsened by correlated complications such as aspiration pneumonia, oral infections, dental caries, and maceration of the skin. Diverse therapeutic approaches have been proposed for the treatment of sialorrhea, including surgery and the use of anticholinergic agents, with limited results and the possible occurrence of serious adverse events...
November 9, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27910767/immunostimulatory-effects-of-melphalan-and-usefulness-in-adoptive-cell-therapy-with-antitumor-cd4-t-cells
#13
Michal Kuczma, Zhi-Chun Ding, Gang Zhou
The alkylating agent melphalan is used in the treatment of hematological malignancies, especially multiple myeloma. In the past, the usefulness of melphalan has been solely attributed to its cytotoxicity on fastgrowing cancerous cells. Although the immunomodulatory effects of melphalan were suggested many years ago, only recently has this aspect of melphalan's activity begun to be elucidated at the molecular level. Emerging evidence indicates that melphalan can foster an immunogenic microenvironment by inducing immunogenic cell death (ICD) as characterized by membrane translocation of endoplasmic reticulum protein calreticulin (CRT) and by release of chromatin-binding protein high-mobility group box 1 (HMGB1)...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27910742/review-article-fabricated-microparticles-an-innovative-method-to-minimize-the-side-effects-of-nsaids-in-arthritis
#14
Shaivad Shabee Hulhasan Abadi, Afrasim Moin, Gangadharappa Hosahalli Veerabhadrappa
Microparticles are polymeric bodies ranging 1-1000 µm that constitute a variety of forms such as microcapsules, microspheres, microcages, microshells, microrods, biosensors microparticles, radiolabeled microparticles, and so forth. This review focuses on general microparticles, mainly microcapsules and microspheres. Nonsteriodal anti-inflammatory drugs (NSAIDs) are one of the mostcommonly prescribed medications in the world. Most of the NSAIDs available have severe side effects. With increased awareness of NSAID-induced gastrointestinal (GI) side effects, safety has become a priority in treatment of arthritis and other inflammatory diseases with NSAIDs...
2016: Critical Reviews in Therapeutic Drug Carrier Systems
https://www.readbyqxmd.com/read/27909065/cdk5-directly-targets-nuclear-p21cip1-and-promotes-cancer-cell-growth
#15
Pao-Hsuan Huang, Mei-Chih Chen, Yu-Ting Peng, Wei-Hsiang Kao, Chih-Hsiang Chang, Yun-Chi Wang, Chih-Ho Lai, Jer-Tsong Hsieh, Jo-Hsin Wang, Yueh-Tsung Lee, Eugene Lin, Chia-Herng Yue, Hsin-Yi Wang, Shuen-Chi You, Ho Lin
The significance of Cdk5 in cell-cycle control and cancer biology has gained increased attention. Here we report the inverse correlation between the protein levels of Cdk5 and p21(CIP1) from cell-based and clinical analysis. Mechanistically, we identify that Cdk5 overexpression triggers the proteasome-dependent degradation of p21(CIP1) through a S130 phosphorylation in a Cdk2-independent manner. Besides, the evidence from cell-based and clinical analysis shows that Cdk5 primarily regulates nuclear p21(CIP1) protein degradation...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27907031/in-vitro-pre-clinical-validation-of-suicide-gene-modified-anti-cd33-redirected-chimeric-antigen-receptor-t-cells-for-acute-myeloid-leukemia
#16
Kentaro Minagawa, Muhammad O Jamil, Mustafa Al-Obaidi, Larisa Pereboeva, Donna Salzman, Harry P Erba, Lawrence S Lamb, Ravi Bhatia, Shin Mineishi, Antonio Di Stasi
BACKGROUND: Approximately fifty percent of patients with acute myeloid leukemia can be cured with current therapeutic strategies which include, standard dose chemotherapy for patients at standard risk of relapse as assessed by cytogenetic and molecular analysis, or high-dose chemotherapy with allogeneic hematopoietic stem cell transplant for high-risk patients. Despite allogeneic hematopoietic stem cell transplant about 25% of patients still succumb to disease relapse, therefore, novel strategies are needed to improve the outcome of patients with acute myeloid leukemia...
2016: PloS One
https://www.readbyqxmd.com/read/27906178/a-mechanism-for-overcoming-p-glycoprotein-mediated-drug-resistance-novel-combination-therapy-that-releases-stored-doxorubicin-from-lysosomes-via-lysosomal-permeabilization-using-dp44mt-or-dpc
#17
Nicole A Seebacher, Des R Richardson, Patric J Jansson
The intracellular distribution of a drug can cause significant variability in both activity and selectivity. Herein, we investigate the mechanism by which the anti-cancer agents, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) and the clinically trialed, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), re-instate the efficacy of doxorubicin (DOX), in drug-resistant P-glycoprotein (Pgp)-expressing cells. Both Dp44mT and DpC potently target and kill Pgp-expressing tumors, while DOX effectively kills non-Pgp-expressing cancers...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906171/combined-nifuroxazide-and-sat05f-therapy-reduces-graft-versus-host-disease-after-experimental-allogeneic-bone-marrow-transplantation
#18
Huijie Jia, Tiesuo Zhao, Yinghua Ji, Xiaolong Jia, Wenjing Ren, Chen Li, Minming Li, Yali Xiao, Hui Wang, Kailin Xu
Acute graft-versus-host disease (aGvHD) is the major barrier to the broader use of allogenetic hematopoietic stem cells. However, currently these are no highly specific and efficient drugs. Monotherapy is not sufficient and more efficient and safe therapeutic regimen are urgent need. Studies demonstrated TLR9 and Stat3 signal pathways are critical for antigen-presenting cell maturation and T-cell activation, which are important mediators in aGvHD. Specific block these two critical signal pathways using their inhibitors SAT05f and nifuroxazide may be the novel strategies for aGvHD therapy...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906000/the-antiviral-compound-bit225-inhibits-hiv-1-replication-in-myeloid-dendritic-cells
#19
Gabriela Khoury, Gary Ewart, Carolyn Luscombe, Michelle Miller, John Wilkinson
BACKGROUND: Previous studies with BIT225 (N-carbamimidoyl-5-(1-methyl-1H-pyrazol-4-yl)-2-naphthamide) have demonstrated a unique antiviral activity that blocks the release of HIV-1 from monocyte-derived macrophages (MDM). Antagonising the ion channel formed by HIV-1 Vpu, BIT225 preferentially targets de novo intracellular virus produced in 'virus-containing compartments' of MDM. In primary infections, dendritic cells (DC) are one of the first cells infected by HIV-1 and can transfer virus to more permissive CD4(+) T cells, making these cells an important target for novel antiviral therapies...
February 8, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27905556/cellular-aspartyl-proteases-promote-the-unconventional-secretion-of-biologically-active-hiv-1-matrix-protein-p17
#20
Francesca Caccuri, Maria Luisa Iaria, Federica Campilongo, Kristen Varney, Alessandro Rossi, Stefania Mitola, Silvia Schiarea, Antonella Bugatti, Pietro Mazzuca, Cinzia Giagulli, Simona Fiorentini, Wuyuan Lu, Mario Salmona, Arnaldo Caruso
The human immune deficiency virus type 1 (HIV-1) matrix protein p17 (p17), although devoid of a signal sequence, is released by infected cells and detected in blood and in different organs and tissues even in HIV-1-infected patients undergoing successful combined antiretroviral therapy (cART). Extracellularly, p17 deregulates the function of different cells involved in AIDS pathogenesis. The mechanism of p17 secretion, particularly during HIV-1 latency, still remains to be elucidated. A recent study showed that HIV-1-infected cells can produce Gag without spreading infection in a model of viral latency...
December 1, 2016: Scientific Reports
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