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https://www.readbyqxmd.com/read/28735481/single-cell-mass-cytometry-of-acute-myeloid-leukemia-and-leukemia-stem-progenitor-cells
#1
Zhihong Zeng, Marina Konopleva, Michael Andreeff
Mass cytometry time-of-flight (CyTOF) empowers us to understand acute myeloid leukemia (AML) biology at the single-cell level. This technology, combined with advanced data-analysis methods, enables identification and characterization of the rare AML stem/progenitor cells that play key roles in drug resistance and AML relapse. Here we provide a protocol for AML sample preparation for CyTOF and keynotes emphasizing critical steps in and troubleshooting strategies for this procedure.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28735350/inflammatory-joint-disorders-and-neutrophilic-dermatoses-a-comprehensive-review
#2
REVIEW
Massimo Cugno, Roberta Gualtierotti, Pier Luigi Meroni, Angelo Valerio Marzano
Rheumatoid arthritis and spondyloarthritis are inflammatory joint disorders with an autoimmune pathogenesis and systemic involvement. The skin is one of the most frequently affected extraarticular sites with a number of manifestations or distinct diseases, including common conditions, such as rheumatoid nodules and psoriasis, and rare diseases like neutrophilic dermatoses. The latter are clinically characterised by polymorphic lesions, including pustules, bullae, abscesses, papules, nodules, plaques and ulcers, and histologically by neutrophil-rich inflammatory infiltrates...
July 22, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28735187/progress-in-targeting-the-bcl-2-family-of-proteins
#3
REVIEW
Thomas P Garner, Andrea Lopez, Denis E Reyna, Adam Z Spitz, Evripidis Gavathiotis
The network of protein-protein interactions among the BCL-2 protein family plays a critical role in regulating cellular commitment to mitochondrial apoptosis. Anti-apoptotic BCL-2 proteins are considered promising targets for drug discovery and exciting clinical progress has stimulated intense investigations in the broader family. Here, we discuss recent developments in small molecules targeting anti-apoptotic proteins and alternative approaches to targeting BCL-2 family interactions. These studies advance our understanding of the role of BCL-2 family proteins in physiology and disease, providing unique tools for dissecting these functions...
July 20, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28735109/design-and-rationale-for-a-real-world-observational-cohort-of-patients-with-nonalcoholic-fatty-liver-disease-the-target-nash-study
#4
A Sidney Barritt, Norman Gitlin, Samuel Klein, Anna S Lok, Rohit Loomba, Laura Malahias, Margaret Powell, Miriam B Vos, L Michael Weiss, Kenneth Cusi, Brent A Neuschwander-Tetri, Arun Sanyal
Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and can lead to cirrhosis, hepatocellular carcinoma, and end-stage liver disease. NAFLD comprises the spectrum from simple steatosis (nonalcoholic fatty liver, NAFL), to steatosis with inflammation (nonalcoholic steatohepatitis, NASH). Current primary therapy recommended for NAFLD is weight loss induced by lifestyle modification. The difficulty in achieving this has led to robust pharmacological therapy development. While new drugs may show efficacy in selected phase II/III clinical trial populations, their real-world effectiveness is unknown...
July 19, 2017: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/28735028/protein-only-antimicrobial-peptide-containing-recombinant-nanoparticles-with-inherent-built-in-antibacterial-activity
#5
Naroa Serna, Laura Sánchez-García, Alejandro Sánchez-Chardi, Ugutz Unzueta, Mónica Roldán, Ramón Mangues, Esther Vázquez, Antonio Villaverde
The emergence of bacterial antibiotic resistances is a serious concern in human and animal health. In this context, naturally occurring cationic antimicrobial peptides (AMPs) might play a main role in a next generation of drugs against bacterial infections. Taking an innovative approach to design self-organizing functional proteins, we have generated here protein-only nanoparticles with intrinsic AMP microbicide activity. Using a recombinant version of the GWH1 antimicrobial peptide as building block, these materials show a wide antibacterial activity spectrum in absence of detectable toxicity on mammalian cells...
July 19, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28735000/application-of-pharmacometrics-and-quantitative-systems-pharmacology-to-cancer-therapy-the-example-of-luminal-a-breast-cancer
#6
REVIEW
Brett Fleisher, Kayla Andrews, Ashley A Brown, Sihem Ait-Oudhia
Breast cancer (BC) is the most common cancer in women, and the second most frequent cause of cancer-related deaths in women worldwide. It is a heterogeneous disease composed of multiple subtypes with distinct morphologies and clinical implications. Quantitative systems pharmacology (QSP) is an emerging discipline bridging systems biology with pharmacokinetics (PK) and pharmacodynamics (PD) leveraging the systematic understanding of drugs' efficacy and toxicity. Despite numerous challenges in applying computational methodologies for QSP and mechanism-based PK/PD models to biological, physiological, and pharmacological data, bridging these disciplines has the potential to enhance our understanding of complex disease systems such as BC...
July 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28734860/the-expanding-field-of-biologics-in-the-management-of-chronic-urticaria
#7
Shyam Joshi, David A Khan
Chronic urticaria (CU) is the occurrence of urticaria with or without angioedema for at least 6 weeks. Management has traditionally involved antihistamines as first-line therapy with various alternative therapies for refractory cases. Largely based on the success of biologics for various diseases, this class of drugs has come to the forefront of medical research. The first and only Food and Drug Administration-approved biologic for the management of CU is omalizumab (humanized anti-IgE mAb). In the past decade, a substantial amount of research has been centered on the mechanism of action, efficacy, dosing, and safety of omalizumab...
July 19, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28734675/safety-and-effectiveness-of-tocilizumab-in-treating-patients-with-rheumatoid-arthritis-a-three-year-study-in-taiwan
#8
Ching-Tsai Lin, Wen-Nan Huang, Chia-Wei Hsieh, Yi-Ming Chen, Der-Yuan Chen, Tsu-Yi Hsieh, Yi-Hsing Chen
OBJECTIVE: To evaluate the long-term safety and effectiveness of tocilizumab (TCZ) for the treatment of rheumatoid arthritis (RA) in a real-world clinical setting in Taiwan. METHOD: All refractory RA patients who initiated intravenous TCZ between August 2012 and March 2015 were enrolled. Data on patient characteristics, drug safety and effectiveness were collected. RESULTS: A total of 114 RA patients were recruited. Despite the majority of them (93%) had previous biologic failure, 43...
July 1, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28734206/theoretical-investigation-of-the-conformational-space-of-baicalin
#9
Juan J Martínez Medina, Evelina G Ferrer, Patricia A M Williams, Nora B Okulik
Flavonoids are a large group of polyphenolic compounds ubiquitously present in plants. They are important components of human diet. They are recognized as potential drug candidates to be used in the treatment and prevention of a lot of pathological disorders, due to their protective effects. Baicalin (7-glucuronic acid 5, 6-dihydroxyflavone) is one of the main single active constituents isolated from the dried roots of Scutellaria baicalensis Georgi. The great interest on this flavonoid is due to its various pharmacological properties, such as antioxidant, antimicrobial, anti-inflammatory, anticancer and so on, and its high accumulation in the roots of S...
July 11, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28734051/a-user-s-guide-for-%C3%AE-synuclein-biomarker-studies-in-biological-fluids-perianalytical-considerations
#10
REVIEW
Brit Mollenhauer, Richard Batrla, Omar El-Agnaf, Douglas R Galasko, Hilal A Lashuel, Kalpana M Merchant, Lesley M Shaw, Dennis J Selkoe, Robert Umek, Hugo Vanderstichele, Henrik Zetterberg, Jing Zhang, Chelsea Caspell-Garcia, Chris Coffey, Samantha J Hutten, Mark Frasier, Peggy Taylor
Parkinson's disease biomarkers are needed to increase diagnostic accuracy, to objectively monitor disease progression and to assess therapeutic efficacy as well as target engagement when evaluating novel drug and therapeutic strategies. This article summarizes perianalytical considerations for biomarker studies (based on immunoassays) in Parkinson's disease, with emphasis on quantifying total α-synuclein protein in biological fluids. Current knowledge and pitfalls are discussed, and selected perianalytical variables are presented systematically, including different temperature of sample collection and types of collection tubes, gradient sampling, the addition of detergent, aliquot volume, the freezing time, and the different thawing methods...
July 22, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28733914/molecular-and-functional-analysis-of-monoclonal-antibodies-in-support-of-biologics-development
#11
REVIEW
Xin Wang, Zhiqiang An, Wenxin Luo, Ningshao Xia, Qinjian Zhao
Monoclonal antibody (mAb)-based therapeutics are playing an increasingly important role in the treatment or prevention of many important diseases such as cancers, autoimmune disorders, and infectious diseases. Multi-domain mAbs are far more complex than small molecule drugs with intrinsic heterogeneities. The critical quality attributes of a given mAb, including structure, post-translational modifications, and functions at biomolecular and cellular levels, need to be defined and profiled in details during the developmental phases of a biologics...
July 21, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28733904/polyamines-therapeutic-perspectives-in-oxidative-stress-and-inflammatory-diseases
#12
REVIEW
Tarique Hussain, Bie Tan, Wenkai Ren, Najma Rahu, Rahim Dad, Dildar Hussain Kalhoro, Yulong Yin
Polyamines are naturally occurring aliphatic compounds, particularly essential elements for biological functions. These compounds play a central role in regulating molecular pathways which are responsible for cellular proliferation, growth, and differentiation. Importantly, excessive polyamine catabolism can lead to a prominent source of oxidative stress which increases inflammatory response and thought to be involved in several diseases including stroke, renal failure, neurological disease, liver disease, and even cancer...
July 21, 2017: Amino Acids
https://www.readbyqxmd.com/read/28733524/arginine-auxotrophic-gene-signature-in-paediatric-sarcomas-and-brain-tumours-provides-a-viable-target-for-arginine-depletion-therapies
#13
Ashley Vardon, Madhumita Dandapani, Daryl Cheng, Paul Cheng, Carmela De Santo, Francis Mussai
Paediatric sarcomas and brain tumours, remain cancers of significant unmet need, with a poor prognosis for patients with high risk disease or those who relapse, and significant morbidities from treatment for those that survive using standard treatment approaches. Novel treatment strategies, based on the underlying tumour biology, are needed to improve outcomes. Arginine is a semi-essential amino acid that is imported from the extracellular microenvironment or recycled from intracellular precursors through the combined expression of the enzymes ornithine transcarbamylase (OTC), argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL) enzymes...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733378/is-it-time-to-change-the-type-2-diabetes-treatment-paradigm-no-metformin-should-remain-the-foundation-therapy-for-type-2-diabetes
#14
Silvio E Inzucchi
Most treatment guidelines, including those from the American Diabetes Association/European Association for the Study of Diabetes and the International Diabetes Federation, suggest metformin be used as the first-line therapy after diet and exercise. This recommendation is based on the considerable body of evidence that has accumulated over the last 30 years, but it is also supported on clinical grounds based on metformin's affordability and tolerability. As such, metformin is the most commonly used oral antihyperglycemic agent in the U...
August 2017: Diabetes Care
https://www.readbyqxmd.com/read/28733377/is-it-time-to-change-the-type-2-diabetes-treatment-paradigm-yes-glp-1-ras-should-replace-metformin-in-the-type-2-diabetes-algorithm
#15
Muhammad Abdul-Ghani, Ralph A DeFronzo
Most treatment guidelines, including those from the American Diabetes Association/European Association for the Study of Diabetes and the International Diabetes Federation, suggest metformin be used as the first-line therapy after diet and exercise. This recommendation is based on the considerable body of evidence that has accumulated over the last 30 years, but it is also supported on clinical grounds based on metformin's affordability and tolerability. As such, metformin is the most commonly used oral antihyperglycemic agent in the U...
August 2017: Diabetes Care
https://www.readbyqxmd.com/read/28733206/omics-based-identification-of-the-combined-effects-of-idiosyncratic-drugs-and-inflammatory-cytokines-on-the-development-of-drug-induced-liver-injury
#16
J Jiang, K Mathijs, L Timmermans, S M Claessen, A Hecka, J Weusten, R Peters, J H van Delft, J C S Kleinjans, D G J Jennen, T M de Kok
The mechanisms of idiosyncratic drug-induced hepatotoxicity remain largely unclear. It has demonstrated that the drug idiosyncrasy is potentiated in the context of inflammation and intracellular ceramides may play a role in this process. To study the mechanisms, HepG2 cells were co-treated with high and low doses of three idiosyncratic (I) and three non-idiosyncratic (N) compounds, with (I+ and N+) or without (I- and N-) a cytokine mix. Microarray, lipidomics and flow cytometry were performed to investigate the genome-wide expression patterns, the intracellular ceramide levels and the induction of apoptosis...
July 18, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28733187/a-confidence-building-exercise-in-data-and-identifiability-modeling-cancer-chemotherapy-as-a-case-study
#17
Marisa C Eisenberg, Harsh V Jain
Mathematical modeling has a long history in the field of cancer therapeutics, and there is increasing recognition that it can help uncover the mechanisms that underlie tumor response to treatment. However, making quantitative predictions with such models often requires parameter estimation from data, raising questions of parameter identifiability and estimability. Even in the case of structural (theoretical) identifiability, imperfect data and the resulting practical unidentifiability of model parameters can make it difficult to infer the desired information, and in some cases, to yield biologically correct inferences and predictions...
July 18, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28732927/ultrasound-promoted-dispersive-micro-solid-phase-extraction-of-trace-anti-hypertensive-drugs-from-biological-matrices-using-a-sonochemically-synthesized-conductive-polymer-nanocomposite
#18
Maryam Hemmati, Maryam Rajabi, Alireza Asghari
In this work, a rapid and efficient procedure named ultrasound meliorated dispersive micro solid-phase extraction followed by high performance liquid chromatography-ultra violet detection (US-D-μSPE-HPLC-UV) was developed for the pre-concentration of the main trace anti-hypertensive drugs in complex matrices. The basis of this procedure was a polypyrrole-sodium dodecylbenzenesulfonate/zinc oxide (PPy-DBSNa/ZnO) nanocomposite. It was readily synthesized by the impressive way of in situ sonochemical oxidative polymerization in the presence of some additives such as FeCl3 and DBSNa, ultimately leading to the effective coating of PPy on the ZnO nanoparticle cores...
November 2017: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/28732370/silibinin-an-old-drug-for-hematological-disorders
#19
REVIEW
Hai Zou, Xing-Xing Zhu, Guo-Bing Zhang, Yuan Ma, Yi Wu, Dong-Sheng Huang
Silibinin (silybin), a non-toxic natural polyphenolic flavonoid, is the principal and the most biologically active component of silymarin. It is efficient in the treatment of acute and chronic liver disorders caused by toxins, drug, alcohol, hepatitis, and gall bladder disorders. Further, in our previous studies, we explored the anti-cancer efficacy in common cancers, such as lung, prostatic, colon, breast, bladder, as well as, hepatocellular carcinoma. Interestingly, silibinin is still not solely limited to the treatment of these diseases...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732311/solid-and-aqueous-magnetoliposomes-as-nanocarriers-for-a-new-potential-drug-active-against-breast-cancer
#20
Ana Rita O Rodrigues, Pedro M F Mendes, Pedro M L Silva, V A Machado, Bernardo G Almeida, J P Araújo, Maria-João R P Queiroz, Elisabete M S Castanheira, Paulo J G Coutinho
Iron oxide nanoparticles, with diameters around 12nm, were synthesized by coprecipitation method. The magnetic properties indicate a superparamagnetic behavior with a coercive field of 9.7Oe and a blocking temperature of 118K. Both aqueous and solid magnetoliposomes containing magnetite nanoparticles have sizes below 150nm, suitable for biomedical applications. Interaction between both types of magnetoliposomes and models of biological membranes was proven. A new antitumor compound, a diarylurea derivative of thienopyridine, active against breast cancer, was incorporated in both aqueous and solid magnetoliposomes, being mainly located in the lipid membrane...
July 8, 2017: Colloids and Surfaces. B, Biointerfaces
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