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https://www.readbyqxmd.com/read/28186996/harnessing-rna-sequencing-for-global-unbiased-evaluation-of-two-new-adjuvants-for-dendritic-cell-immunotherapy
#1
Till S M Mathan, Johannes Textor, Annette E Sköld, Inge Reinieren-Beeren, Tom van Oorschot, Mareke Brüning, Carl G Figdor, Sonja I Buschow, Ghaith Bakdash, I Jolanda M de Vries
Effective stimulation of immune cells is crucial for the success of cancer immunotherapies. Current approaches to evaluate the efficiency of stimuli are mainly defined by known flow cytometry-based cell activation or cell maturation markers. This method however does not give a complete overview of the achieved activation state and may leave important side effects unnoticed. Here, we used an unbiased RNA sequencing (RNA-seq)-based approach to compare the capacity of four clinical-grade dendritic cell (DC) activation stimuli used to prepare DC-vaccines composed of various types of DC subsets; the already clinically applied GM-CSF and Frühsommer meningoencephalitis (FSME) prophylactic vaccine and the novel clinical grade adjuvants protamine-RNA complexes (pRNA) and CpG-P...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28151905/impact-of-patient-and-treatment-characteristics-on-glycemic-control-and-hypoglycemia-in-patients-with-type-2-diabetes-initiated-to-insulin-glargine-or-nph-a-post-hoc-pooled-patient-level-analysis-of-6-randomized-controlled-trials
#2
Francesca Porcellati, Jay Lin, Paola Lucidi, Geremia B Bolli, Carmine G Fanelli
BACKGROUND: The goal of this post hoc analysis was to determine key patient and treatment-related factors impacting glycosylated hemoglobin (A1C) and hypoglycemia in patients with uncontrolled type 2 diabetes who were initiated to basal insulin (neutral protamine Hagedorn [NPH] or glargine). METHODS: Using individual patient-level data pooled from 6 treat-to-target trials, 2600 patients with type 2 diabetes on oral antidiabetic agents initiated to insulin glargine or NPH and treated for 24 to 36 weeks were analyzed...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28150359/potential-role-of-tracing-stem-cell-transplantation-and-effects-on-the-immune-cell-function-of-ferumoxytol-combining-with-heparin-and-protamine-in-vivo-in-vitro
#3
Jingyuan Zhao, Xin Guan, Yang Liu, Hua Piao, Rutao Liu, Xiang Zhou, Bo Sun, Yue Du, Jing Liu
Cell labeling and tracing have played an increasingly important role in the field of stem cell transplantation. Nanocomplexes combining three Food and Drug Administration (FDA)-approved drugs: heparin (H), protamine (P) and ferumoxytol (F)(HPF nanocomplexes) display high labeling efficiency in human adipose tissue-derived stem cells (hADSCs), but their biological safety has not been determined. In this study, we tested the labeling efficiency of HPF in hADSCs through in vitro cytotoxicity studies and in vivo murine preclinical studies using HPF-labeled hADSCs...
February 2, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28131717/aptamer-functionalized-hybrid-nanoparticle-for-the-treatment-of-breast-cancer
#4
David Powell, Sruti Chandra, Kyra Dodson, Farhana Shaheen, Kylar Wilt, Shubha Ireland, Muniruzzaman Syed, Srikanta Dash, Thomas Wiese, Tarun Mandal, Anup Kundu
PURPOSE: Resistance to chemotherapeutic agents such as doxorubicin is a major reason for cancer treatment failure. At present the treatment option for metastatic breast cancer is very poor. Therefore, development of an effective therapeutic strategy to circumvent MDR of metastatic breast cancer is highly anticipated. The MDR of metastatic breast cancer cells was accompanied with the overexpression of P-gp transporter. Even though the overexpression of P-gp could be minimized by silencing with siRNA, the question is how they can be selectively targeted to the cancer cells...
January 25, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28105735/observational-registry-of-basal-insulin-treatment-orbit-in-patients-with-type-2-diabetes-uncontrolled-with-oral-antihyperglycaemic-drugs-real-life-use-of-basal-insulin-in-china
#5
Linong Ji, Puhong Zhang, Dongshan Zhu, Xian Li, Jiachao Ji, Juming Lu, Xiaohui Guo, Weiping Jia, Jianping Weng, Yangfeng Wu, Wenying Yang, Dajin Zou, Zhiguang Zhou, Changyu Pan, Yan Gao, Satish K Garg
AIMS: To examine treatment patterns following basal insulin (BI) introduction in type 2 diabetes mellitus (T2DM) patients under real-world conditions across China. MATERIALS AND METHODS: Overall, 18,995 patients inadequately controlled [HbA1c ≥ 53 mmol/mol (7%)] with oral antihyperglycaemic drugs (OADs) and willing to receive BI treatment were registered at 209 hospitals and followed at baseline (visit 1), 3 months (visit 2), and 6 months (visit 3). Type of BI was initiated at physicians' discretion...
January 20, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28098662/management-of-a-patient-with-antiphospholipid-syndrome-undergoing-aortic-valve-replacement-using-the-hepcon-hemostasis-management-system-plus-and-rotational-thromboelastometry-a-case-report
#6
Yuriko Samejima, Mitsuharu Kodaka, Junko Ichikawa, Tetsu Mori, Kazuyoshi Ando, Keiko Nishiyama, Makiko Komori
A 72-year-old woman with antiphospholipid syndrome underwent aortic valve replacement. Her preoperative activated partial thromboplastin time was 61.7 seconds and activated clotting time was 219 seconds. During cardiopulmonary bypass, the Hepcon Hemostasis Management System (HMS) Plus determined the heparin dose needed to maintain whole-body heparin at 3 U/mL. After cardiopulmonary bypass, 100 mg of protamine was administered based on heparin-protamine neutralization, and the activated clotting time decreased...
January 16, 2017: A & A Case Reports
https://www.readbyqxmd.com/read/28092788/patient-level-meta-analysis-of-efficacy-and-hypoglycaemia-in-people-with-type-2-diabetes-initiating-insulin-glargine-100u-ml-or-neutral-protamine-hagedorn-insulin-analysed-according-to-concomitant-oral-antidiabetes-therapy
#7
David R Owens, Louise Traylor, Peter Mullins, Wolfgang Landgraf
AIMS: Evaluate efficacy and hypoglycaemia according to concomitant oral antidiabetes drug (OAD) in people with type 2 diabetes initiating insulin glargine 100U/mL (Gla-100) or neutral protamine Hagedorn (NPH) insulin once daily. METHODS: Four studies (target fasting plasma glucose [FPG] ⩽100mg/dL [⩽5.6mmol/L]; duration ⩾24weeks) were included. Standardised data from 2091 subjects (Gla-100, n=1024; NPH insulin, n=1067) were analysed. Endpoints included glycated haemoglobin (HbA1c) and FPG change, glycaemic target achievement, hypoglycaemia, weight change, and insulin dose...
November 9, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28090458/efficient-isolation-of-sperm-with-high-dna-integrity-and-stable-chromatin-packaging-by-a-combination-of-density-gradient-centrifugation-and-magnetic-activated-cell-sorting
#8
Hee-Jun Chi, Su-Jin Kwak, Seok-Gi Kim, Youn-Young Kim, Ji-Young Park, Chang-Seok Yoo, Il-Hae Park, Hong-Gil Sun, Jae-Won Kim, Kyeong-Ho Lee
OBJECTIVE: This study was carried out to investigate the correlations of the sperm DNA fragmentation index (DFI) with semen parameters and apoptosis, and to investigate the effects of density-gradient centrifugation (DGC) and magnetic-activated cell sorting (MACS) on reducing the proportion of sperm with DNA fragmentation and protamine deficiency. METHODS: Semen analysis and a sperm DNA fragmentation assay were performed to assess the correlations between semen parameters and the DFI in 458 semen samples...
December 2016: Clinical and Experimental Reproductive Medicine
https://www.readbyqxmd.com/read/28076980/status-of-sperm-born-oocyte-activating-factors-pawp-plc%C3%AE-and-sperm-chromatin-in-uncapacitated-capacitated-and-acrosome-reacted-conditions
#9
Marziyeh Tavalaee, Kazem Parivar, Abdol-Hossein Shahverdi, Kamran Ghaedi, Mohammad Hossein Nasr-Esfahani
The aim of this study was to investigate the value of sperm factors PAWP and PLCζ involved in oocyte activation and sperm chromatin status, as indicators of sperm quality during uncapacitated, capacitated and acrosome-reacted conditions. Semen samples collected from 10 normozoospermic men and sperm factors PAWP, PLCζ, protamine deficiency and DNA fragmentation evaluated in fresh samples, processed sample by DGC (density gradient centrifugation), capacitated and acrosome reacted sperm, using immunofluorescence and flow cytometry...
January 12, 2017: Human Fertility: Journal of the British Fertility Society
https://www.readbyqxmd.com/read/28074788/comparison-of-two-doses-of-heparin-on-outcome-in-off-pump-coronary-artery-bypass-surgery-patients-a-prospective-randomized-control-study
#10
Murali Chakravarthy, Dattatreya Prabhakumar, Patil Thimmannagowda, Jayaprakash Krishnamoorthy, Antony George, Vivek Jawali
INTRODUCTION: While off pump coronary artery bypass surgery is practiced with an intention to reduce the morbidity associated with cardiopulmonary bypass, the resultant 'hypercoagulability' needs to be addressed. Complications such as cavitary thrombus possibly due to the hyper coagulability after off pump coronary artery bypass surgery have been described. Many clinicians use higher doses of heparin - up to 5 mg/kg in order to thwart this fear. Overall, there appears to be no consensus on the dose of heparin in off pump coronary artery bypass surgeries...
January 2017: Annals of Cardiac Anaesthesia
https://www.readbyqxmd.com/read/28067593/characteristics-of-proteinaceous-additives-in-stabilizing-enzymes-during-freeze-thawing-and-drying
#11
Takanori Shimizu, Tamayo Korehisa, Hiroyuki Imanaka, Naoyuki Ishida, Koreyoshi Imamura
Protein-stabilizing characteristics of sixteen proteins during freeze-thawing and freeze-drying were investigated. Five enzymes, each with different instabilities against freezing and dehydration, were employed as the protein to be stabilized. Proteinaceous additives generally resulted in greater enzyme stabilization during freeze-thawing than sugars while the degree of stabilization for basic lysozyme and protamine were inferior to that of neutral and acidic proteins. Freeze-drying-induced inactivation of enzyme was also reduced by the presence of a proteinaceous additive, the extent of which was lower than that for a sugar...
January 9, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28067489/fluorescent-strips-of-electrospun-fibers-for-ratiometric-sensing-of-serum-heparin-and-urine-trypsin
#12
Long Zhao, Tao Wang, Qiang Wu, Yuan Liu, Zhoujiang Chen, Xiaohong Li
"Turn-on" or "turn-off" probes remain challenges in the establishment of sensitive, easily operated, and reliable methods for in situ monitoring bioactive substances. In the current study, electrospun fibrous strips are designed to provide straightforward observations of ratiometric color changes with the naked eye in the presence of serum heparin or urine trypsin. A tetraphenylethene (TPE) derivative is constructed and along with phloxine B is grafted on fibers, followed by protamine adsorption to induce static quenching of phloxine B and aggregation-induced emission of the TPE derivative...
February 1, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28063135/cost-effectiveness-of-insulin-degludec-plus-liraglutide-ideglira-in-a-fixed-combination-for-uncontrolled-type-2-diabetes-mellitus-in-sweden
#13
Åsa Ericsson, Adam Lundqvist
BACKGROUND: Patients with uncontrolled type 2 diabetes mellitus (T2DM) are a priority group for intensified therapy without weight gain and with low risk of hypoglycaemia. OBJECTIVE: This study evaluates the cost effectiveness of insulin degludec plus liraglutide (IDegLira, Xultophy(®)) compared with six potential intensification treatment options for patients with T2DM that is uncontrolled with basal insulin. METHODS: The Swedish Institute for Health Economics (IHE) Cohort Model of Type 2 Diabetes was used with Swedish input data, a 40-year time frame and a societal perspective...
January 6, 2017: Applied Health Economics and Health Policy
https://www.readbyqxmd.com/read/28054764/two-step-assembling-of-near-infrared-off-on-fluorescent-nanohybrids-for-synchronous-tumor-imaging-and-microrna-modulation-based-therapy
#14
Xiongwei Deng, Zhaoxia Yin, Jianqing Lu, Yang Xia, Leihou Shao, Qin Hu, Zhixiang Zhou, Fang Zhang, Shaomei Zhou, Yan Wu, Wang Sheng, Yi Zeng
Theranostic nanoparticles with combined imaging and therapy functions show great promise in cancer precision medicine. In this study, we constructed near-infrared (NIR) "OFF-ON" fluorescent nanohybrids (F-PNDs) for synchronous tumor imaging and microRNA (miRNA) modulation therapy against esophageal cancer. Nanodiamond clusters (NDs) were first functionalized for protamine sulfate immobilization (PNDs) on their surfaces via a noncovalent self-assembling approach and simultaneous encapsulation of NIR emitting fluorescence dye cyanine 5 (Cy-5) (F-PNDs)...
February 1, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28050628/epigenetic-modifications-and-reprogramming-in-paternal-pronucleus-sperm-preimplantation-embryo-and-beyond
#15
REVIEW
Yuki Okada, Kosuke Yamaguchi
Pronuclear/zygotic stage is the very first stage of life. In this period, paternal pronucleus undergoes massive chromatin remodeling called "paternal reprogramming" including protamine-histone replacement and subsequent acquisition of epigenetic modifications. Although these consecutive events are required for the initiation of maternal-zygotic transition, the precise role of paternal reprogramming and its effect on subsequent embryonic development has been largely unknown to date. Recently, various new techniques, especially next-generation sequencing (NGS) and RNAi microinjection contribute to unveil the epigenetic transition from both paternal and maternal to early preimplantation embryos, suggesting not only the simple transcriptional regulation by transcription factors but also dynamic structural alteration of chromatin to initiate the wave of zygotic gene transcription...
January 3, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28040490/biological-effects-of-iron-oxide-protamine-sulfate-complex-on-mesenchymal-stem-cells-and-its-relaxometry-based-labeling-optimization-for-cellular-mri
#16
Sushanta Kumar Mishra, Subash Khushu, Gurudutta Gangenahalli
Mesenchymal stem cells (MSCs) are frequently used as a therapeutic, but reliable imaging technique to longitudinally evaluate the engraftment of transplanted cells is inadequate. For magnetic resonance imaging (MRI), it is essential to understand the technical competence of in vitro stem cells labeling with iron oxide with regard to its relaxation behavior and significance of its biological expressions. The purpose of the study was to optimize the effective labeling of MSCs with high transverse relaxivity iron oxide contrast agent with protamine sulfate and also evaluate the biological effects (phenotype and function) of labeled MSCs...
December 28, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/28040350/improved-treatment-satisfaction-in-patients-with-type-1-diabetes-treated-with-insulin-glargine-100u-ml-versus-neutral-protamine-hagedorn-insulin-an-exploration-of-key-predictors-from-two-randomized-controlled-trials
#17
William Polonsky, Louise Traylor, Ling Gao, Wenhui Wei, Barbara Ameer, Andreas Stuhr, Aleksandra Vlajnic
AIM: Investigate contributors to treatment satisfaction in type 1 diabetes (T1D). METHODS: Post-hoc analysis using the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) in 771 T1D patients from two 28-week trials comparing once-daily insulin glargine 100U/mL (Gla-100) with once- or twice-daily NPH neutral protamine Hagedorn (NPH) insulin. RESULTS: Gla-100 was associated with a significant improvement in treatment satisfaction versus NPH (overall population adjusted mean [standard error] DTSQs change from baseline: +1...
December 8, 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28034889/alteration-of-blood-clotting-and-lung-damage-by-protamine-are-avoided-using-the-heparin-and-polyphosphate-inhibitor-uhra
#18
Manu Thomas Kalathottukaren, Libin Abraham, Piyushkumar R Kapopara, Benjamin F L Lai, Rajesh A Shenoi, Federico I Rosell, Edward M Conway, Edward L G Pryzdial, James H Morrissey, Charles A Haynes, Jayachandran N Kizhakkedathu
Anticoagulant therapy associated bleeding and pathological thrombosis, pose serious risks to hospitalized patients. Both complications could be mitigated by developing new therapeutics that safely neutralize anticoagulant activity and inhibit activators of the intrinsic blood clotting pathway, such as polyphosphate (polyP) and extracellular nucleic acids. The latter strategy could reduce the use of anticoagulants, potentially decreasing bleeding events. However, previously described cationic inhibitors of polyP and extracellular nucleic acids, exhibit both non-specific binding and adverse effects on blood clotting that limit their use...
December 29, 2016: Blood
https://www.readbyqxmd.com/read/28031247/thioredoxin-dependent-disulfide-bond-reduction-is-required-for-protamine-eviction-from-sperm-chromatin
#19
Alexander V Emelyanov, Dmitry V Fyodorov
Cysteine oxidation in protamines leads to their oligomerization and contributes to sperm chromatin compaction. Here we identify the Drosophila thioredoxin Deadhead (DHD) as the factor responsible for the reduction of intermolecular disulfide bonds in protamines and their eviction from sperm during fertilization. Protamine chaperone TAP/p32 dissociates DNA-protamine complexes in vitro only when protamine oligomers are first converted to monomers by DHD. dhd-null embryos cannot decondense sperm chromatin and terminate development after the first pronuclear division...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28026957/comparison-of-avidin-neutravidin-and-streptavidin-as-nanocarriers-for-efficient-sirna-delivery
#20
Akshay Jain, Ashutosh Barve, Zhen Zhao, Wei Jin, Kun Cheng
Protein-based drug delivery carrier has been one of the most employed modalities in the biopharmaceuticals. In this study, we have compared avidin and its two analogues, neutravidin and streptavidin, as nanocarriers for the delivery of biotin-labeled siRNA with the help of biotinylated cholesterol (targeting ligand) and protamine (condensing agent). These proteins have similar binding affinity to biotin but substantially difference in their physical and chemical characteristics. Here, we have shown how these characteristics affect the size, cellular uptake and activity of the avidin-based siRNA nanocomplex...
December 27, 2016: Molecular Pharmaceutics
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