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https://www.readbyqxmd.com/read/28922428/diminished-neutrophil-extracellular-trap-net-formation-is-a-novel-innate-immune-deficiency-induced-by-acute-ethanol-exposure-in-polymicrobial-sepsis-which-can-be-rescued-by-cxcl1
#1
Liliang Jin, Sanjay Batra, Samithamby Jeyaseelan
Polymicrobial sepsis is the result of an exaggerated host immune response to bacterial pathogens. Animal models and human studies demonstrate that acute alcohol intoxication is a key risk factor for sepsis-induced mortality. Multiple chemokines, such as CXCL1, CXCL2 and CXCL5 are critical for neutrophil recruitment and proper function of neutrophils. However, it is not quite clear the mechanisms by which acute alcohol suppresses immune responses and whether alcohol-induced immunosuppression can be rescued by chemokines...
September 18, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28922349/cytochrome-p450-and-flavin-containing-monooxygenase-families-age-dependent-differences-in-expression-and-functional-activity
#2
Nicole R Zane, Yao Chen, Michael Zhuo Wang, Dhiren R Thakker
BACKGROUND: Age-dependent differences in pharmacokinetics exist for metabolically cleared medications. Differential contributions in the cytochrome P450 3A (CYP3A), CYP2C, and flavin-containing monooxygenases (FMO) families play an important role in the metabolic clearance of a large number of drugs administered to children. METHODS: Unlike previous semi-quantitative characterization of age-dependent changes in the expression of genes and proteins (Western Analysis), this study quantifies both gene and absolute protein expression in the same fetal, pediatric and adult hepatic tissue...
September 18, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28922323/face-graft-scaffold-production-in-a-rat-model
#3
Jérôme Duisit, Hadrien Amiel, Giuseppe Orlando, Adeline Dedriche, Catherine Behets, Pierre Gianello, Benoît Lengelé
BACKGROUND: As a route towards face bioengineering, our group previously reported the production of a complete scaffold production by perfusion-decellularization of a porcine ear subunit graft and partial recellularization. In order to extend the scaffold to the whole face and to down-scale it, we applied our findings to a rodent hemi-facial graft model. METHODS: After euthanasia, seven full-thickness rat hemi-face grafts were harvested with the CCA and the EJV as pedicle, and cannulated...
September 14, 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28922313/lateral-perturbation-induced-stepping-strategies-and-predictors-in-persons-poststroke
#4
Vicki L Gray, Chieh-Ling Yang, Sandy McCombe Waller, Mark W Rogers
BACKGROUND AND PURPOSE: Falls commonly occur as weight is transferred laterally, and impaired reactive stepping responses are associated with falls after stroke. The purpose of this study was to examine differences in and the determinants of mediolateral (M-L) protective stepping strategies when pulled off balance toward the paretic and nonparetic sides. METHODS: Eighteen individuals more than 6 months poststroke were pulled in the M-L direction by a lateral waist-pull perturbation system...
October 2017: Journal of Neurologic Physical Therapy: JNPT
https://www.readbyqxmd.com/read/28922150/synthesis-radiosynthesis-and-preliminary-in-vitro-and-in-vivo-evaluation-of-the-fluorinated-ceramide-trafficking-inhibitor-hpa-12-for-brain-applications
#5
Simone M Crivelli, Andreas Paulus, Jozef Markus, Matthias Bauwens, Dusan Berkes, Helga E De Vries, Monique T Mulder, Jochen Walter, Felix M Mottaghy, Mario Losen, Pilar Martinez-Martinez
Ceramide levels are increased in blood and brain tissue of Alzheimer's disease (AD) patients. Since the ceramide transporter protein (CERT) is the only known protein able to mediate non-vesicular transfer of ceramide between organelle membranes, the modulation of CERT function may impact on ceramide accumulation. The competitive CERT inhibitor N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl) dodecanamide (HPA-12) interferes with ceramide trafficking. To understand the role of ceramide/CERT in AD, HPA-12 can be a useful tool to modulate ceramide trafficking...
September 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28921760/genome-wide-association-study-of-a-nicotine-metabolism-biomarker-in-african-american-smokers-impact-of-chromosome-19-genetic-influences
#6
Meghan J Chenoweth, Jennifer J Ware, Andy Z X Zhu, Christopher B Cole, Lisa Sanderson Cox, Nikki Nollen, Jasjit S Ahluwalia, Neal L Benowitz, Robert A Schnoll, Larry W Hawk, Paul M Cinciripini, Tony P George, Caryn Lerman, Joanne Knight, Rachel F Tyndale
BACKGROUND AND AIMS: The activity of CYP2A6, the major nicotine-inactivating enzyme, is measurable in smokers using the nicotine metabolite ratio (NMR; 3'hydroxycotinine/cotinine). Due to its role in nicotine clearance, the NMR is associated with smoking behaviours and response to pharmacotherapies. The NMR is highly heritable (~80%), and on average lower in African Americans (AA) versus Whites. We previously identified several reduce and loss-of-function CYP2A6 variants common in individuals of African descent...
September 16, 2017: Addiction
https://www.readbyqxmd.com/read/28921690/tissue-specific-and-time-dependent-clonal-expansion-of-enu-induced-mutant-cells-in-gpt-delta-mice
#7
Takafumi Nakayama, Tomoko Sawai, Ikuko Masuda, Shinya Kaneko, Kazumi Yamauchi, Benjamin J Blyth, Yoshiya Shimada, Akira Tachibana, Shizuko Kakinuma
DNA mutations play a crucial role in the origins of cancer, and the clonal expansion of mutant cells is one of the fundamental steps in multistage carcinogenesis. In this study, we correlated tumor incidence in B6C3F1 mice during the period after exposure to N-ethyl-N-nitrosourea (ENU) with the persistence of ENU-induced mutant clones in transgenic gpt delta B6C3F1 mice. The induced gpt mutations afforded no selective advantage in the mouse cells and could be distinguished by a mutational spectrum that is characteristic of ENU treatment...
September 16, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28921650/antibody-drug-conjugates-as-cancer-therapeutics-past-present-and-future
#8
Heather E Vezina, Monette Cotreau, Tae H Han, Manish Gupta
Antibody-drug conjugates (ADCs) represent an innovative therapeutic approach that provides novel treatment options and hope for patients with cancer. By coupling monoclonal antibodies (mAbs) to cytotoxic small-molecule payloads with a plasma-stable linker, ADCs offer the potential for increased drug specificity and fewer off-target effects than systemic chemotherapy. As evidence for the potential of these therapies, many new ADCs are in various stages of clinical development. Because their structure poses unique challenges to pharmacokinetic and pharmacodynamic characterization, it is critical to recognize the differences between ADCs and conventional chemotherapy in the design of ADC clinical development strategies...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921624/pharmacodynamics-and-pharmacokinetics-of-ticagrelor-versus-clopidogrel-in-patients-with-acute-coronary-syndromes-and-chronic-kidney-disease
#9
Heyang Wang, Jing Qi, Yi Li, Yunbiao Tang, Chao Li, Jing Li, Yaling Han
BACKGROUND: Pivotal clinical trials found ticagrelor reduced ischemic complications to a greater extent than clopidogrel and what is more, the benefit gradually increased with the reduction on creatinine clearance. However, the underlying mechanisms remains poorly explored. METHODS: This is a single-center, prospective, randomized clinical trial involving 60 hospitalized P2Y12 inhibitor naïve patients with CKD (eGFR<60ml/min/1.73m(2) ) and NSTE-ACS. Eligible patients were randomly assigned in a 1:1 ratio to receive ticagrelor(180 mg loading dose, then 90 mg twice daily followed) or clopidogrel(600 mg loading dose, then 75 mg qd followed)...
September 15, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921585/allergooncology-opposite-outcomes-of-immune-tolerance-in-allergy-and-cancer
#10
E Jensen-Jarolim, H J Bax, R Bianchini, S Crescioli, T R Daniels-Wells, D Dombrowicz, E Fiebiger, H J Gould, S Irshad, J Janda, D H Josephs, F Levi-Schaffer, L O Mahony, G Pellizzari, M L Penichet, F Redegeld, F Roth-Walter, J Singer, E Untersmayr, L Vangelista, S N Karagiannis
While desired for the cure of allergy, regulatory immune cell subsets and non-classical Th2-biased inflammatory mediators in the tumour microenvironment can contribute to immune suppression and escape of tumours from immunological detection and clearance. A key aim in the cancer field is therefore to design interventions that can break immunological tolerance and halt cancer progression, whereas on the contrary allergen immunotherapy exactly aims to induce tolerance. In this position paper, we review insights on immune tolerance derived from allergy and from cancer inflammation, focusing on what is known about the roles of key immune cells and mediators...
September 16, 2017: Allergy
https://www.readbyqxmd.com/read/28921554/dj-1-deficiency-impairs-autophagy-and-reduces-alpha-synuclein-phagocytosis-by-microglia
#11
Yuval Nash, Eran Schmukler, Dorit Trudler, Ronit Pinkas-Kramarski, Dan Frenkel
Parkinson's disease (PD) is a progressive neurodegenerative disorder, of which 1% of the hereditary cases are linked to mutations in DJ-1, an oxidative stress sensor. The pathological hallmark of PD is intercellular inclusions termed Lewy Bodies, composed mainly of α-Synuclein (α-Syn) protein. Recent findings have shown that α-Syn can be transmitted from cell to cell, suggesting an important role of microglia, as the main scavenger cells of the brain, in clearing α-Syn. We previously reported that the knock down (KD) of DJ-1 in microglia increased cells' neurotoxicity to dopaminergic neurons...
September 16, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28921501/immunological-tolerance-to-lcmv-antigens-differently-affects-control-of-acute-and-chronic-virus-infection-in-mice
#12
Christina Woopen, Tobias Straub, Oliver Schweier, Ulrike Aichele, Katharina Düker, Thomas Boehm, Hanspeter Pircher
Cytotoxic T lymphocytes (CTLs) play a key role in the control of lymphocytic choriomeningitis virus (LCMV) infection. In C57BL/6 mice (H-2(b) ), the CTL response is mainly directed against epitopes from the LCMV glycoprotein (GP) and the nucleoprotein (NP) which represent the two major viral proteins. The role of GP- versus NP-derived epitopes for viral clearance was examined using transgenic (tg) mice ubiquitously expressing LCMV GP and NP, respectively. These mice lack GP- or NP-specific CTLs and show decreased levels of GP- or NP-specific antibodies as a result of tolerance induction...
August 11, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28921470/cgas-sting-activation-in-the-tumor-microenvironment-and-its-role-in-cancer-immunity
#13
Geneviève Pépin, Michael P Gantier
Stimulator of interferon (IFN) genes (STING) is a key mediator in the immune response to cytoplasmic DNA sensed by cyclic GMP-AMP (cGAMP) synthase (cGAS). After synthesis by cGAS, cGAMP acts as a second messenger activating STING in the cell harboring cytoplasmic DNA but also in adjacent cells through gap junction transfer. While the role of the cGAS-STING pathway in pathogen detection is now well established, its importance in cancer immunity has only recently started to emerge. Nonetheless, STING appears to be an essential component in the recruitment of immune cells to the tumor microenvironment, which is paramount to immune clearance of the tumor...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28921442/preparation-of-immunoliposomes-by-direct-coupling-of-antibodies-based-on-a-thioether-bond
#14
Raquel Petrilli, Josimar O Eloy, Robert J Lee, Renata F V Lopez
Drug delivery is of paramount importance, since the drug needs to be delivered to a specific site, in adequate concentration, avoiding degradation in order to provide therapeutic efficacy. Different nanocarriers have been used over the years for this purpose and liposomes are well-established systems due to the high biocompatibility and the possibility to vehiculate both hydrophilic and lipophilic drugs. In order to circumvent the rapid clearance by the reticuloendothelial system and to avoid the healthy cells exposure to the drug, long circulating liposomes containing polyethyleneglycol (PEG) and functionalized liposomes for targeted delivery have been developed...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28920925/expression-of-piwi-protein-miwi2-defines-a-distinct-population-of-multiciliated-cells
#15
Gregory A Wasserman, Aleksander D Szymaniak, Anne C Hinds, Kazuko Yamamoto, Hirofumi Kamata, Nicole Ms Smith, Kristie L Hilliard, Claudia Carrieri, Adam T Labadorf, Lee J Quinton, Xingbin Ai, Xaralabos Varelas, Felicia Chen, Joseph P Mizgerd, Alan Fine, Dónal O'Carroll, Matthew R Jones
P-element-induced wimpy testes (Piwi) proteins are known for suppressing retrotransposon activation in the mammalian germline. However, whether Piwi protein or Piwi-dependent functions occur in the mammalian soma is unclear. Contrary to germline-restricted expression, we observed that Piwi-like Miwi2 mRNA is indeed expressed in epithelial cells of the lung in adult mice and that it is induced during pneumonia. Further investigation revealed that MIWI2 protein localized to the cytoplasm of a discrete population of multiciliated airway epithelial cells...
September 18, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28920918/mice-deficient-for-erad-machinery-component-sel1l-develop-central-diabetes-insipidus
#16
Daniel G Bichet, Yoann Lussier
Deficiency of the antidiuretic hormone arginine vasopressin (AVP) underlies diabetes insipidus, which is characterized by the excretion of abnormally large volumes of dilute urine and persistent thirst. In this issue of the JCI, Shi et al. report that Sel1L-Hrd1 ER-associated degradation (ERAD) is responsible for the clearance of misfolded pro-arginine vasopressin (proAVP) in the ER. Additionally, mice with Sel1L deficiency, either globally or specifically within AVP-expressing neurons, developed central diabetes insipidus...
September 18, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28920588/%C3%AE-%C3%AE-t-cells-in-homeostasis-and-host-defence-of-epithelial-barrier-tissues
#17
REVIEW
Morten M Nielsen, Deborah A Witherden, Wendy L Havran
Epithelial surfaces line the body and provide a crucial interface between the body and the external environment. Tissue-resident epithelial γδ T cells represent a major T cell population in the epithelial tissues and are ideally positioned to carry out barrier surveillance and aid in tissue homeostasis and repair. In this Review, we focus on the intraepithelial γδ T cell compartment of the two largest epithelial tissues in the body - namely, the epidermis and the intestine - and provide a comprehensive overview of the crucial contributions of intraepithelial γδ T cells to tissue integrity and repair, host homeostasis and protection in the context of the symbiotic relationship with the microbiome and during pathogen clearance...
September 18, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28920466/annals-express-evaluation-of-common-paediatric-creatinine-based-glomerular-filtration-rate-gfr-estimating-equations-in-black-african-children-in-kwazulu-natal-south-africa
#18
Yashna Rampursat, Rajendra Bhimma, Elaene Naicker, Fozy Peer, Verena Gounden
Background The use of serum creatinine (S-Cr) equations for estimating glomerular filtration rate (GFR) is well known in adults and children. We evaluated the revised Schwartz creatinine based estimated GFR (eGFR) prediction equation in Black African children in KwaZulu-Natal, South Africa. Methods Review of medical records of all Black African patients aged 2-18 years old who have had GFR determined by intravenous Technetium-99m-diethylene-triamine-pentaacetate((9)(9)(m)Tc DTPA), for the period 1 January 2010 to 31 December 2014 at the Inkosi Albert Luthuli Central Hospital (IALCH), Durban, South Africa was performed...
January 1, 2017: Annals of Clinical Biochemistry
https://www.readbyqxmd.com/read/28920097/acute-cd47-blockade-during-ischemic-myocardial-reperfusion-enhances-phagocytosis-associated-cardiac-repair
#19
Shuang Zhang, Xin-Yi Yeap, Matthew DeBerge, Nivedita K Naresh, Kevin Wang, Zhengxin Jiang, Jane E Wilcox, Steven M White, John P Morrow, Paul W Burridge, Daniel Procissi, Evan A Scott, William Frazier, Edward B Thorp
Our data suggest that, after a myocardial infarction, integrin-associated protein CD47 on cardiac myocytes is elevated. In culture, increased CD47 on the surface of dying cardiomyocytes impairs phagocytic removal by immune cell macrophages. After myocardial ischemia and reperfusion, acute CD47 inhibition with blocking antibodies enhanced dead myocyte clearance by cardiac phagocytes and also improved the resolution of cardiac inflammation, reduced infarct size, and preserved cardiac contractile function. Early targeting of CD47 in the myocardium after reperfusion may be a new strategy to enhance wound repair in the ischemic heart...
August 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28920077/mimicking-the-bioactivity-of-fibroblast-growth-factor-2-using-supramolecular-nanoribbons
#20
Charles M Rubert Pérez, Zaida Álvarez, Feng Chen, Taner Aytun, Samuel I Stupp
Fibroblast growth factor (FGF-2) is a multifunctional growth factor that has pleiotropic effects in different tissues and organs. In particular, FGF-2 has a special role in angiogenesis, an important process in development, wound healing, cell survival, and differentiation. Therefore, incorporating biological agents like FGF-2 within therapeutic biomaterials is a potential strategy to create angiogenic bioactivity for the repair of damaged tissue caused by trauma or complications that arise from age and/or disease...
September 11, 2017: ACS Biomaterials Science & Engineering
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