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https://www.readbyqxmd.com/read/27926828/harnessing-cancer-cell-metabolism-for-theranostic-applications-using-metabolic-glycoengineering-of-sialic-acid-in-breast-cancer-as-a-pioneering-example
#1
REVIEW
Haitham A Badr, Dina M M AlSadek, Motawa E El-Houseini, Christopher T Saeui, Mohit P Mathew, Kevin J Yarema, Hafiz Ahmed
Abnormal cell surface display of sialic acids - a family of unusual 9-carbon sugars - is widely recognized as distinguishing feature of many types of cancer. Sialoglycans, however, typically cannot be identified with sufficiently high reproducibility and sensitivity to serve as clinically accepted biomarkers and similarly, almost all efforts to exploit cancer-specific differences in sialylation signatures for therapy remain in early stage development. In this report we provide an overview of important facets of glycosylation that contribute to cancer in general with a focus on breast cancer as an example of malignant disease characterized by aberrant sialylation...
November 25, 2016: Biomaterials
https://www.readbyqxmd.com/read/27926762/association-of-arterial-and-lymph-node-inflammation-with-distinct-inflammatory-pathways-in-human-immunodeficiency-virus-infection
#2
Ahmed Tawakol, Amorina Ishai, Danny Li, Richard A P Takx, Sophia Hur, Yannick Kaiser, Miguel Pampaloni, Adam Rupert, Denise Hsu, Irini Sereti, Rémi Fromentin, Nicolas Chomont, Peter Ganz, Steven G Deeks, Priscilla Y Hsue
Importance: Human immunodeficiency virus (HIV) infection is associated with a high risk of cardiovascular disease and increased arterial inflammation. In HIV, inflammation is also increased within lymph nodes (LNs), tissues known to harbor the virus even among treated and suppressed individuals. Objective: To test the hypothesis that arterial inflammation is linked to HIV disease activity and to inflammation within HIV-infected tissues (LNs). Design, Setting, and Participants: For this case-control study, participants were recruited from the SCOPE (Observational Study of the Consequences of the Protease Inhibitor Era) cohort, a clinic-based cohort of individuals receiving care at San Francisco General Hospital and the San Francisco Veteran's Affairs Medical Center...
December 7, 2016: JAMA Cardiology
https://www.readbyqxmd.com/read/27925643/primary-and-secondary-hemophagocytic-lymphohistiocytosis-have-different-patterns-of-t-cell-activation-differentiation-and-repertoire
#3
Sandra Ammann, Kai Lehmberg, Udo Zur Stadt, Gritta Janka, Anne Rensing-Ehl, Christian Klemann, Maximilian Heeg, Sebastian Bode, Ilka Fuchs, Stephan Ehl
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening inflammatory syndrome characterized by hyperactivation of lymphocytes and histiocytes. T cells play a key role in HLH pathogenesis, but their differentiation pattern is not well characterized in patients with active HLH. We compared T-cell activation patterns between patients with familial HLH (1°HLH), 2°HLH without apparent infectious trigger (2°HLH) and 2°HLH induced by a viral infection (2°V-HLH). Polyclonal CD8(+) T cells are highly activated in 1°HLH and 2°V-HLH, but less in 2°HLH as assessed by HLA-DR expression and marker combination with CD45RA, CCR7, CD127, PD-1 and CD57...
December 7, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27925318/total-synthesis-of-the-mycobacterium-tuberculosis-dideoxymycobactin-838-and-stereoisomers-diverse-cd1a-restricted-t-cells-display-a-common-hierarchy-of-lipopeptide-recognition
#4
Janice Cheng, Ligong Liu, Daniel Pellicci, Scott Jj Reddiex, Rachel Cotton, Tan-Yun Cheng, David Young, Ildiko Van Rhijn, Branch Moody, Jamie Rossjohn, David Fairlie, Dale Godfrey, Spencer John Williams
Mycobacterium tuberculosis produces dideoxymycobactin-838 (DDM-838), a lipopeptide that potently activates T cells upon binding to the MHC-like antigen-presenting molecule CD1a. M. tuberculosis produces DDM-838 in only trace amounts and a previous solid-phase synthesis provided sub-milligram quantities. We describe a high yielding solution-phase synthesis of DDM-838 that features a Mitsunobu substitution that avoids yield-limiting epimerization at lysine during esterification, and amidation conditions that prevent double-bond isomerization of the Z-C20:1 acyl chain, and provides material with equivalent antigenicity to natural DDM-838...
December 7, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27923824/human-dendritic-cells-mitigate-nk-cell-dysfunction-mediated-by-nonselective-jak%C3%A2-blockade
#5
Shane A Curran, Justin A Shyer, Erin T St Angelo, Lillian R Talbot, Sneh Sharma, David J Chung, Glenn Heller, Katharine C Hsu, Brian C Betts, James W Young
Janus kinase (JAK) inhibitors have achieved positive responses in myeloproliferative neoplasms, but at the expense of decreased natural killer (NK) cell numbers and compromised function. Selective JAK2 inhibition may also have a role in preventing and treating graft-vs-host disease after allogeneic hematopoietic stem cell transplantation. Although JAK inhibitors can impair monocyte-derived dendritic cell (moDC) activation and function and suppress effector T-cell responses, the effects on NK cells and the relevant mechanisms remain undefined...
December 6, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27923697/layer-by-layer-nanoparticle-platform-for-cancer-active-targeting
#6
Min Sung Suh, Jie Shen, Liisa T Kuhn, Diane J Burgess
Nanoparticles as drug delivery carriers have been investigated over the last few decades, particularly for cancer treatment. The rationale in developing such nanoparticles is to maximize drug efficacy while minimizing toxic side effects. This can be most effectively achieved through target specific drug delivery. A novel biocompatible nanoparticle platform prepared using the core-shell self-assembly technique is reported. The core consists of calcium phosphate which is biocompatible and pH-sensitive, and the shell is composed of biocompatible polymers (hyaluronic acid, CD44 targeting moiety; and chitosan, physical cross-linker)...
December 3, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27922332/effect-of-moderate-and-high-intensity-chronic-exercise-on-the-pancreatic-islet-morphometry-in-healthy-rats-bdnf-receptor-participation
#7
Alberto Jiménez-Maldonado, Adolfo Virgen-Ortiz, Valery Melnikov, Alejandrina Rodríguez-Hernández, Armando Gamboa-Domínguez, Sergio Montero, Jesús Muñiz-Murguía, Mónica Lemus, Elena Roces de Álvarez-Buylla
A B S T R A C T The function and morphology of β-cells is largely dependent on insulin demand. As β-cells cover a bigger cell proportion in pancreas islets, changes of insulin producer cells affect the whole pancreatic islet morphology. Growth factors as the neurotrophins regulate the pancreas physiology, besides; physical exercise increases insulin sensitivity, and further modifies brain derived neurotrophic factor (BDNF) concentration in plasma. The aim of this study was to investigate the effects of chronic exercise (running in a treadmill for eight weeks) intensity on pancreatic islet morphometry in healthy state...
December 6, 2016: Islets
https://www.readbyqxmd.com/read/27921406/house-dust-mites-confer-a-distinct-immunological-feature-among-dermatitis
#8
Safa Baris, Ahmet Ozen, Tuba Akdeniz, Elif Karakoc-Aydiner, Ovgu Aydin, Hulya Ercan, Ismail Ogulur, Yildiz Camcioglu, Reha Cengizlier, Cuyan Demirkesen, Deniz Yucelten, Gulderen Demirel, Isil B Barlan
Atopic dermatitis (AD) is a heterogeneous disease with regard to clinical phenotype and natural history. We investigated T cell subtypes and cytokine responses in peripheral blood and skin lesions of AD patients with various sensitivities. Immunological studies were performed in 27 subjects: 9 house dust mite (HDM)-sensitized; 6 subjects with sensitizations other than HDM; 7 non-allergic AD patients and 5 healthy controls. Among those, skin biopsy samples of 13 subjects were evaluated for immunohistochemical analyses, as well...
August 2016: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/27920123/selective-enhancement-of-insulin-sensitivity-in-the-endothelium-in-vivo-reveals-a-novel-proatherosclerotic-signalling-loop
#9
Hema Viswambharan, Nadira Y Yuldasheva, Anshuman Sengupta, Helen Imrie, Matthew C Gage, Natalie J Haywood, Andrew M Walker, Anna Skromna, Natalia Makova, Stacey L Galloway, Pooja Shah, Piruthivi Sukumar, Karen E Porter, Peter J Grant, Ajay M Shah, Celio X Santos, Jing Li, David J Beech, Stephen Wheatcroft, Richard M Cubbon, Mark T Kearney
RATIONALE: In the endothelium, insulin stimulates endothelial nitric oxide synthase (eNOS) to generate the anti-atherosclerotic signalling radical NO. Insulin resistant type 2 diabetes is associated with reduced NO availability and accelerated atherosclerosis. The effect of enhancing endothelial insulin sensitivity on NO availability is unclear. OBJECTIVE: To answer this question we generated a mouse with endothelial cell (EC)-specific over-expression of the human insulin receptor (hIRECO) using the Tie2 promoter-enhancer...
December 5, 2016: Circulation Research
https://www.readbyqxmd.com/read/27919190/investigation-of-the-influence-of-glycyrrhizin-on-the-pharmacokinetics-of-celastrol-in-rats-using-lc-ms-and-its-potential-mechanism
#10
Guangkui Yan, Hanhua Zhang, Wei Wang, Yuan Li, Chenghuang Mao, Mingqiao Fang, Xianhong Yi, Jingdong Zhang
1. The aim of this study was to investigate the effects of glycyrrhizin on the pharmacokinetics of celastrol in rats. 2. Twelve male Sprague-Dawley rats were randomly assigned to two groups: control group and test group. Test group was pretreated with glycyrrhizin at a dose of 100 mg/kg/day for 10 days, and then the two groups were orally administered with celastrol at a dose of 1 mg/kg. The concentration of celastrol was determined using a sensitive and reliable LC-MS method. 3. The results showed that glycyrrhizin could significantly decrease the plasma concentration (from 64...
December 5, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/27918544/a-balance-between-elongation-and-trimming-regulates-telomere-stability-in-stem-cells
#11
Teresa Rivera, Candy Haggblom, Sandro Cosconati, Jan Karlseder
Telomere length maintenance ensures self-renewal of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs); however, the mechanisms governing telomere length homeostasis in these cell types are unclear. Here, we report that telomere length is determined by the balance between telomere elongation, which is mediated by telomerase, and telomere trimming, which is controlled by XRCC3 and Nbs1, homologous recombination proteins that generate single-stranded C-rich telomeric DNA and double-stranded telomeric circular DNA (T-circles), respectively...
December 5, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27917702/effectiveness-of-pegaspargase-gemcitabine-and-oxaliplatin-p-gemox-chemotherapy-combined-with-radiotherapy-in-newly-diagnosed-stage-ie-to-iie-nasal-type-extranodal-natural-killer-t-cell-lymphoma
#12
Wen Wei, Ping Wu, Li Li, Zhi-Hui Zhang
PURPOSE: Extranodal natural killer/T-cell lymphoma (ENKTL), nasal-type, is a distinct subtype of non-Hodgkin lymphoma. ENKTL is sensitive to radiotherapy, but the prognosis is poorer than those of other types of early stage lymphoma. To date, optimal treatment strategies for patients with early stage ENKTL have not been fully defined. METHODS: We retrospectively investigated the efficacy and safety of pegaspargase, gemcitabine, and oxaliplatin (P-GEMOX) combined with different dose radiotherapy (RT) in the treatment of 35 newly diagnosed, stage IE to IIE ENKTL patients at our institution from October 2011 to September 2015...
December 5, 2016: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/27917296/stat1-associated-intratumoural-th1-immunity-predicts-chemotherapy-resistance-in-high-grade-serous-ovarian-cancer
#13
Katrina K Au, Cécile Le Page, Runhan Ren, Liliane Meunier, Isabelle Clément, Kathrin Tyrishkin, Nichole Peterson, Jennifer Kendall-Dupont, Timothy Childs, Julie-Ann Francis, Charles H Graham, Andrew W Craig, Jeremy A Squire, Anne-Marie Mes-Masson, Madhuri Koti
High-grade serous ovarian carcinoma (HGSC) accounts for 70% of all epithelial ovarian cancers but clinical management is challenged by a lack of accurate prognostic and predictive biomarkers of chemotherapy response. This study evaluated the role of Signal Transducer and Activator of Transcription 1 (STAT1) as an independent prognostic and predictive biomarker and its correlation with intratumoural CD8(+) T cells in a second independent biomarker validation study. Tumour STAT1 expression and intratumoural CD8(+) T cell infiltration were assessed by immunohistochemistry as a multicentre validation study conducted on 734 chemotherapy-naïve HGSCs...
October 2016: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/27916705/newborn-screening-for-severe-combined-immunodeficiency-using-a-novel-and-simplified-method-to-measure-t-cell-excision-circles-trec
#14
Laura Tagliaferri, Joachim B Kunz, Margit Happich, Susanna Esposito, Thomas Bruckner, Daniel Hübschmann, Jürgen G Okun, Georg F Hoffmann, Ansgar Schulz, Judit Kappe, Carsten Speckmann, Martina U Muckenthaler, Andreas E Kulozik
The prognosis of children with severe combined immunodeficiency (SCID) depends on a presymptomatic diagnosis and early treatment before complications occur. We established and tested a simplified, practical and economic newborn screening method based on the quantification of T-cell receptor excision circles (TRECs) on dried blood spots (DBSs) through qPCR. Our method was validated by the analysis of 11 positive controls, which all showed an absence of TRECs, thus yielding a sensitivity of 100%. Further, we analyzed 6034 anonymized newborns of whom 6031 (99,95%) showed a normal TREC qPCR with a median of 600 estimated TREC copies/1...
December 1, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27916586/selaginella-uncinata-flavonoids-ameliorated-ovalbumin-induced-airway-inflammation-in-a-rat-model-of-asthma
#15
Bing Yu, Wei Cai, Huan-Huan Zhang, Yu-Sen Zhong, Jie Fang, Wen-You Zhang, Li Mo, Lu-Chen Wang, Chen-Huan Yu
ETHNOPHARMACOLOGICAL RELEVANCE: Selaginella uncinata (Desv.) Spring, known as "Cuiyuncao" is a perennial herb widely distributed in the Southeast Asian countries. In the folk medicine, the local minority commonly use it to treat cough and asthma for centuries. AIM OF THE STUDY: This study was carried out to investigate the protective mechanisms of total flavonoids from S. uncinata (SUF) on airway hyperresponsiveness, cytokine release and bitter taste receptors (T2Rs) signaling with emphasis on inflammatory responses in a rat model of ovalbumin (OVA)-induced asthma...
December 1, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27916272/regulation-and-function-of-anaphylatoxins-and-their-receptors-in-allergic-asthma
#16
Yves Laumonnier, Anna V Wiese, Julia Figge, Christian Karsten
Allergic asthma is a disease of the airways driven by maladaptive T helper 2 (Th2) and Th17 immune response against harmless, airborne substances. The hallmarks of this disease are airway hyperresponsiveness (AHR), eosinophilic and neutrophilic airway inflammation and mucus overproduction. Distinct dendric cell (DC) subsets together with airway epithelial and pulmonary vascular endothelial cells play critical roles in allergen sensing and in driving T cell differentiation towards Th2 and Th17 effector or regulatory T cells (Treg)...
December 1, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27914707/adiponectin-alters-renal-calcium-and-phosphate-excretion-through-regulation-of-klotho-expression
#17
Joseph M Rutkowski, Johanne Pastor, Kai Sun, Sun K Park, I Alexandru Bobulescu, Christopher T Chen, Orson W Moe, Philipp E Scherer
The kidney controls systemic calcium and phosphate levels and disturbances of its control mechanisms can lead to a variety of diseases. The insulin-sensitizing adipokine adiponectin is renoprotective and accelerates functional recovery following renal injury. However, unlike other adipokines, adiponectin is reduced in obesity. High adiponectin levels are also correlated with bone loss, suggestive of an additional action in mineral metabolism. Using knockout, wild-type, and adiponectin-overexpressing transgenic mice, we sought to identify the mechanistic basis for adiponectin's ability to regulate calcium and phosphate balance at the level of the kidney...
November 30, 2016: Kidney International
https://www.readbyqxmd.com/read/27914264/pattern-based-sensing-of-triple-negative-breast-cancer-cells-with-dual-ligand-cofunctionalized-gold-nanoclusters
#18
Yu Tao, Mingqiang Li, Debra T Auguste
Early detection of breast cancer is a critical component in patient prognosis and establishing effective therapy regimens. Here, we developed an easily accessible yet potentially powerful sensor to detect cancer cell targets by utilizing seven dual-ligand cofunctionalized gold nanoclusters (AuNCs) as both effective cell recognition elements and signal transducers. On the basis of this AuNC multichannel sensor, we have successfully distinguished healthy, cancerous and metastatic human breast cells with excellent reproducibility and high sensitivity...
November 25, 2016: Biomaterials
https://www.readbyqxmd.com/read/27913566/th2-responses-are-primed-by-skin-dendritic-cells-with-distinct-transcriptional-profiles
#19
Lisa M Connor, Shiau-Choot Tang, Emmanuelle Cognard, Sotaro Ochiai, Kerry L Hilligan, Samuel I Old, Christophe Pellefigues, Ruby F White, Deepa Patel, Adam Alexander T Smith, David A Eccles, Olivier Lamiable, Melanie J McConnell, Franca Ronchese
The dendritic cell signals required for the in vivo priming of IL-4-producing T cells are unknown. We used RNA sequencing to characterize DCs from skin LN of mice exposed to two different Th2 stimuli: the helminth parasite Nippostrongylus brasiliensis (Nb) and the contact sensitizer dibutyl phthalate (DBP)-FITC. Both Nb and DBP-FITC induced extensive transcriptional changes that involved multiple DC subsets. Surprisingly, these transcriptional changes were highly distinct in the two models, with only a small number of genes being similarly regulated in both conditions...
December 2, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27912158/direct-detection-of-phenylephrine-3-o-sulfate-in-ls180-human-intestinal-cells-using-a-novel-hydrophilic-interaction-liquid-chromatography-hilic-assay
#20
Heta N Shah, Matthew T Halquist, Phillip M Gerk
The efficacy of phenylephrine (PE) is controversial due to its extensive pre-systemic metabolism through sulfation to form phenylephrine-3-O-sulfate (PES). Hence quantitation of PES is important in order to study the metabolism of PE. There are no published methods available for direction detection of PES. We have developed and validated a hydrophilic interaction liquid chromatography (HILIC) method for the direct detection of PES and simultaneous detection of PE to study the enzyme kinetics and metabolism of PE to enable approaches to reduce the presystemic metabolism of PE...
November 13, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
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