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Rapid Response System

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https://www.readbyqxmd.com/read/28822039/stimulation-of-nachr%C3%AE-7-receptor-inhibits-tnf-synthesis-and-secretion-in-response-to-lps-treatment-of-mast-cells-by-targeting-erk1-2-and-tace-activation
#1
F Guzmán-Mejía, C López-Rubalcava, C González-Espinosa
The cholinergic anti-inflammatory pathway is recognized as one of the main mechanisms of neuromodulation of the immune system. Activation of the α7 nicotinic acetylcholine receptor (nAchRα7) suppresses cytokine synthesis in distinct immune cells but the molecular mechanisms behind this effect remain to be fully described. Mast cells (MCs) are essential players of allergic reactions and innate immunity responses related to chronic inflammation. Activation of TLR4 receptor in MCs leads to the rapid secretion of pre-synthesized TNF from intracellular pools and to the activation of NFκB, necessary for de novo synthesis of TNF and other cytokines...
August 18, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28821629/effects-of-spaceflight-on-the-muscles-of-the-murine-shoulder
#2
Hua Shen, Chanteak Lim, Andrea G Schwartz, Alexander Andreev-Andrievskiy, Alix C Deymier, Stavros Thomopoulos
Mechanical loading is necessary for the development and maintenance of the musculoskeletal system. Removal of loading via microgravity, paralysis, or bed rest leads to rapid loss of muscle mass and function; however, the molecular mechanisms that lead to these changes are largely unknown, particularly for the spaceflight (SF) microgravity environment. Furthermore, few studies have explored these effects on the shoulder, a dynamically stabilized joint with a large range of motion; therefore, we examined the effects of microgravity on mouse shoulder muscles for the 15-d Space Transportation System (STS)-131, 13-d STS-135, and 30-d Bion-M1 missions...
August 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28819967/enzymatic-peg-poly-amine-co-disulfide-ester-nanoparticles-as-ph-and-redox-responsive-drug-nanocarriers-for-efficient-antitumor-treatment
#3
Ya Chen, Meifei Su, Yingqin Li, Jinbiao Gao, Chao Zhang, Zhong Cao, Jiangbing Zhou, Jie Liu, Zhaozhong Jiang
We have designed and constructed novel multifunctional nanoparticle drug delivery systems that are stable under physiological conditions and responsive to tumor-relevant pH and intracellular reduction potential. The nanoparticles were fabricated from enzymatically synthesized PEG-poly(ω-pentadecalactone-co-N-methyldiethyleneamine-co-3,3'-dithiodipropionate) (PEG-PPMD) and PEG-poly(ε-caprolactone-co-N-methyldiethyleneamine-co-3,3'-dithiodipropionate) (PEG-PCMD) block copolymers via self-assembly processes in aqueous solution...
August 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28819882/novel-immunotherapies-for-multiple-myeloma
#4
REVIEW
Mattia D'Agostino, Mario Boccadoro, Eric L Smith
PURPOSE OF REVIEW: The treatment landscape of multiple myeloma is rapidly changing; however, despite improvement in patients' survival, it still remains a largely incurable disease. One hallmark of myeloma is substantial immune dysfunction leading to an increased infection rate and the inability of immune surveillance to detect neoplastic cells. Here, we critically analyze clinical approaches to harness the immune system to overcome this defect with a focus on antibody based and adoptive cellular therapies...
August 18, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28819844/fourier-ptychographic-microscopy-for-rapid-high-resolution-imaging-of-circulating-tumor-cells-enriched-by-microfiltration
#5
Anthony Williams, Jaebum Chung, Changhuei Yang, Richard J Cote
Examining the hematogenous compartment for evidence of metastasis has increased significantly within the oncology research community in recent years, due to the development of technologies aimed at the enrichment of circulating tumor cells (CTCs), the subpopulation of primary tumor cells that gain access to the circulatory system and are responsible for colonization at distant sites. In contrast to other technologies, filtration-based CTC enrichment, which exploits differences in size between larger tumor cells and surrounding smaller, non-tumor blood cells, has the potential to improve CTC characterization through isolation of tumor cell populations with greater molecular heterogeneity...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28818506/development-and-evaluation-of-%C3%AE-galactosidase-sensitive-antibody-drug-conjugates
#6
Sergii Kolodych, Chloé Michel, Sébastien Delacroix, Oleksandr Koniev, Anthony Ehkirch, Jitka Eberova, Sarah Cianférani, Brigitte Renoux, Wojciech Krezel, Pauline Poinot, Christian D Muller, Sébastien Papot, Alain Wagner
The selective destruction of tumour cells while sparing healthy tissues is one of the main challenges in cancer therapy. Antibody-drug conjugates (ADCs) are arguably the most rapidly expanding class of targeted cancer therapies. Efficient drug conjugation and release technologies are essential for the development of these new therapeutic agents. In response to the ever-increasing demand for efficient drug release systems, we have developed a new class of β-galactosidase-cleavable linkers for ADCs. Within this framework, novel payloads comprising a galactoside linker, the monomethyl auristatin E (MMAE) and cysteine-reactive groups were synthesized, conjugated with trastuzumab and evaluated both in vitro and in vivo...
August 4, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28817806/specialized-mechanosensory-nociceptors-mediating-rapid-responses-to-hair-pull
#7
Nima Ghitani, Arnab Barik, Marcin Szczot, James H Thompson, Chia Li, Claire E Le Pichon, Michael J Krashes, Alexander T Chesler
The somatosensory system provides animals with the ability to detect, distinguish, and respond to diverse thermal, mechanical, and irritating stimuli. While there has been progress in defining classes of neurons underlying temperature sensation and gentle touch, less is known about the neurons specific for mechanical pain. Here, we use in vivo functional imaging to identify a class of cutaneous sensory neurons that are selectively activated by high-threshold mechanical stimulation (HTMRs). We show that their optogenetic excitation evokes rapid protective and avoidance behaviors...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817705/cell-surface-dynamics-and-cellular-distribution-of-endogenous-fcrn
#8
Lena D'Hooghe, Andrew D Chalmers, Sam Heywood, Paul Whitley
A major role for FcRn is the salvage of pinocytosed IgG and albumin from a degradative fate in lysosomes. FcRn achieves this by binding IgG in a pH-dependent manner in acidic endosomes and recycling it to the plasma membrane to be released at neutral pH. This is important in maintaining high serum IgG and albumin levels and has the potential to be exploited to modulate the pharmacokinetics of antibody-based therapeutics. Although FcRn is responsible for the recycling of IgG, the dynamic behaviour of endogenous FcRn is not well understood...
2017: PloS One
https://www.readbyqxmd.com/read/28816340/coagulation-factor-xii-regulates-inflammatory-responses-in-human-lungs
#9
Rosanna Hess, Lukasz Wujak, Christina Hesse, Katherina Sewald, Danny Jonigk, Gregor Warnecke, Hans-Gerd Fieguth, Steven de Maat, Coen Maas, Francesco Bonella, Klaus T Preissner, Benjamin Weiss, Liliana Schaefer, Wolfgang M Kuebler, Philipp Markart, Malgorzata Wygrecka
Increased procoagulant activity in the alveolar compartment and uncontrolled inflammation are hallmarks of the acute respiratory distress syndrome (ARDS). Here, we investigated whether the contact phase system of coagulation is activated and may regulate inflammatory responses in human lungs. Components of the contact phase system were characterized in bronchoalveolar lavage fluids (BALF) from 54 ARDS patients and 43 controls, and their impact on cytokine/chemokine expression in human precision cut lung slices (PCLS) was assessed by a PCR array...
August 17, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28814832/combinatorial-and-sequential-delivery-of-gemcitabine-and-oseltamivir-phosphate-from-implantable-poly-d-l-lactic-co-glycolic-acid-cylinders-disables-human-pancreatic-cancer-cell-survival
#10
Stephanie Allison Logan, Amanda J Brissenden, Myron R Szewczuk, Ronald J Neufeld
Combination therapies against multiple targets are currently being developed to prevent resistance to a single chemotherapeutic agent and to extirpate pre-existing resistance in heterogeneous cancer cells in tumors due to selective pressure from the single agent. Gemcitabine (GEM), a chemotherapeutic agent, is the current standard of care for patients with pancreatic cancer. Patients with pancreatic cancer receiving GEM have a low progression-free survival. Given the poor response rate to GEM, cancer cells are known to develop rapid resistance to this drug...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28814659/fluorescence-detection-of-glutathione-gsh-and-oxidized-glutathione-gssg-in-blood-with-a-nir-excitable-cyanine-probe
#11
Changhui Liu, Fengpei Qi, Fubin Wen, Liping Long, Ronghua Yang
Cyanine has been widely utilized as a near infrared (NIR) fluorophore for detection of glutathione (GSH). However, the excitation of most of the reported cyanine-based probes was less than 800 nm, which inevitably induce biological background absorption and lower the sensitivity, limiting their use for detection of GSH in blood samples. To address this issue, here, a heptamethine cyanine probe (DNIR), with a NIR excitation wavelength at 804 nm and a NIR emission wavelength at 832 nm, is employed for the detection of GSH and its oxidized form (GSSG) in blood...
August 17, 2017: Methods and Applications in Fluorescence
https://www.readbyqxmd.com/read/28813419/vaccine-driven-pharmacodynamic-dissection-and-mitigation-of-fenethylline-psychoactivity
#12
Cody J Wenthur, Bin Zhou, Kim D Janda
Fenethylline, also known by the trade name Captagon, is a synthetic psychoactive stimulant that has recently been linked to a substance-use disorder and 'pharmacoterrorism' in the Middle East. Although fenethylline shares a common phenethylamine core with other amphetamine-type stimulants, it also incorporates a covalently linked xanthine moiety into its parent structure. These independently active pharmacophores are liberated during metabolism, resulting in the release of a structurally diverse chemical mixture into the central nervous system...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813307/the-innate-alarm-system-in-ptsd-conscious-and-subconscious-processing-of-threat
#13
REVIEW
Ruth A Lanius, Daniela Rabellino, Jenna E Boyd, Sherain Harricharan, Paul A Frewen, Margaret C McKinnon
The innate alarm system (IAS), comprised of functionally connected brain regions including the brainstem, amygdala, pulvinar, and frontotemporal cortex, is a fast subcortical brain network facilitating rapid responses to threat. Post-traumatic stress disorder (PTSD) features subconscious and conscious threat detection, together contributing to hyperarousal symptoms. Emerging literature identifies aberrant threat-related neurocircuitry involved in subconscious and conscious threat processing in PTSD. We review this literature, focusing on subconscious threat processing and its relation to the IAS...
April 2017: Current Opinion in Psychology
https://www.readbyqxmd.com/read/28812844/clinician-perspectives-of-barriers-to-effective-implementation-of-a-rapid-response-system-in-an-academic-health-centre-a-focus-group-study
#14
John Rihari-Thomas, Michelle DiGiacomo, Jane Phillips, Phillip Newton, Patricia M Davidson
BACKGROUND: Systemic and structural issues of rapid response system (RRS) models can hinder implementation. This study sought to understand the ways in which acute care clinicians (physicians and nurses) experience and negotiate care for deteriorating patients within the RRS. METHODS: Physicians and nurses working within an Australian academic health centre within a jurisdictional-based model of clinical governance participated in focus group interviews. Verbatim transcripts were analysed using thematic content analysis...
January 1, 2017: International Journal of Health Policy and Management
https://www.readbyqxmd.com/read/28812677/species-specific-responses-to-ocean-acidification-should-account-for-local-adaptation-and-adaptive-plasticity
#15
Cristian A Vargas, Nelson A Lagos, Marco A Lardies, Cristian Duarte, Patricio H Manríquez, Victor M Aguilera, Bernardo Broitman, Steve Widdicombe, Sam Dupont
Global stressors, such as ocean acidification, constitute a rapidly emerging and significant problem for marine organisms, ecosystem functioning and services. The coastal ecosystems of the Humboldt Current System (HCS) off Chile harbour a broad physical-chemical latitudinal and temporal gradient with considerable patchiness in local oceanographic conditions. This heterogeneity may, in turn, modulate the specific tolerances of organisms to climate stress in species with populations distributed along this environmental gradient...
March 13, 2017: Nature ecology & evolution
https://www.readbyqxmd.com/read/28812264/oxytocin-and-steroid-actions
#16
Gustav F Jirikowski, Scott D Ochs, Jack D Caldwell
Biosynthesis and secretion of the hypothalamic nonapeptide oxytocin largely depends on steroid hormones. Estradiol, corticosterone, and vitamin D seem to be the most prominent actors. Due to their lipophilic nature, systemic steroids are thought to be capable of crossing the blood-brain barrier, thus mediating central functions including neuroendocrine and behavioral control. The actual mode of action of steroids in hypothalamic circuitry is still unknown: Most of the oxytocinergic perikarya lack nuclear steroid receptors but express proteins suspected to be membrane receptors for steroids...
August 16, 2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28812000/diagnostic-imaging-features-of-necrotizing-enterocolitis-a-narrative-review
#17
REVIEW
Francesco Esposito, Rosanna Mamone, Marco Di Serafino, Carmela Mercogliano, Valerio Vitale, Gianfranco Vallone, Patrizia Oresta
Necrotizing enterocolitis (NEC) is an inflammatory process, characterized by intestinal necrosis of variable extension, leading to perforation, generalized peritonitis and death. The classical pathogenetic theory focuses on mucosal damage related to a stress induced intestinal ischemia leading to mucosal injury and bacterial colonization of the wall. A more recent hypothesis emphasizes the role of immaturity of gastrointestinal and immune system, particularly of the premature, responsible of bowel wall vulnerability and suffering...
June 2017: Quantitative Imaging in Medicine and Surgery
https://www.readbyqxmd.com/read/28811533/plasma-metabolomics-profiling-of-maintenance-hemodialysis-based-on-capillary-electrophoresis-time-of-flight-mass-spectrometry
#18
Shuxin Liu, Lichao Wang, Chunxiu Hu, Xin Huang, Hong Liu, Qiuhui Xuan, Xiaohui Lin, Xiaojun Peng, Xin Lu, Ming Chang, Guowang Xu
Uremia has been a rapidly increasing health problem in China. Hemodialysis (HD) is the main renal replacement therapy for uremia. The results of large-scale clinical trials have shown that the HD pattern is crucial for long-term prognosis of maintenance hemodialysis (MHD) in uremic patients. Plasma metabolism is very important for revealing the biological insights linked to the therapeutic effects of the HD pattern on uremia. Alteration of plasma metabolites in uremic patients in response to HD therapy has been reported...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811347/tifa-signaling-in-gastric-epithelial-cells-initiates-the-cag-type-4-secretion-system-dependent-innate-immune-response-to-helicobacter-pylori-infection
#19
Alevtina Gall, Ryan G Gaudet, Scott D Gray-Owen, Nina R Salama
Helicobacter pylori is a bacterial pathogen that colonizes the human stomach, causing inflammation which, in some cases, leads to gastric ulcers and cancer. The clinical outcome of infection depends on a complex interplay of bacterial, host genetic, and environmental factors. Although H. pylori is recognized by both the innate and adaptive immune systems, this rarely results in bacterial clearance. Gastric epithelial cells are the first line of defense against H. pylori and alert the immune system to bacterial presence...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28811170/zika-virus-research-models
#20
REVIEW
Jessica L Kublin, James B Whitney
The 2015 Brazilian Zika virus outbreak sparked a rapid response to control the spread of the virus. What was first understood to be a mild self-resolving infection is now linked to significant neurological defects in both neonates, and adults. The WHO declared the 2016 Zika epidemic a public health emergency and issued an unprecedented recommendation to women in affected regions to delay pregnancy until the risks surrounding Zika virus could be understood, or the epidemic contained. Since that time, considerable effort has been dedicated to understanding Zika transmission and pathogenesis to aid the development of drugs and vaccines...
August 12, 2017: Virus Research
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