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https://www.readbyqxmd.com/read/28646631/synthesis-of-novel-and-functionally-selective-non-competitive-muscarinic-antagonists-as-chemical-probes
#1
John F Boulos, Jan Jakubik, John M Boulos, Jelena Momirov, Alena Randakova
Muscarinic receptors are known to play important biological roles and are drug targets for several human diseases. In a pilot study, novel muscarinic antagonists were synthesized and used as chemical probes to obtain additional information of the muscarinic pharmacophore. The design of these ligands made use of current orthosteric and allosteric models of drug-receptor interactions together with chemical motifs known to achieve muscarinic receptor selectivity. This approach has led to the discovery of several non-competitive muscarinic ligands that strongly bind at a secondary receptor site...
June 24, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28645291/the-effect-of-zoledronic-acid-on-type-and-volume-of-modic-changes-among-patients-with-low-back-pain
#2
Katri Koivisto, Jyri Järvinen, Jaro Karppinen, Marianne Haapea, Markus Paananen, Eero Kyllönen, Osmo Tervonen, Jaakko Niinimäki
BACKGROUND: Modic changes (MC) are associated with low back pain (LBP). In this study, we compared changes in size and type of MC, after a single intravenous infusion of 5 mg zoledronic acid (ZA) or placebo, among chronic LBP patients with MC on magnetic resonance imaging (MRI), and evaluated whether the MRI changes correlate with symptoms. METHODS: All patients (N = 19 in ZA, 20 in placebo) had MRI at baseline (0.23-1.5 T) and at one year (1.5-3 T). We evaluated the level, type and volume of all the MC...
June 23, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28643827/anti-oxidant-and-immune-modulatory-properties-of-sulfated-alginate-derivatives-on-human-chondrocytes-and-macrophages
#3
Anne Kerschenmeyer, Øystein Arlov, Vera Malheiro, Matthias Steinwachs, Markus Rottmar, Katharina Maniura-Weber, Gemma Palazzolo, Marcy Zenobi-Wong
Degeneration of articular cartilage represents one of the most common causes of pain and disability in our aging society. Current treatments only address the symptoms of joint disease, but not their underlying causes which include oxidative stress and inflammation in cartilage and surrounding tissues. Sulfated biopolymers that mimic aspects of the native extracellular environment of cartilage are recently gaining interest as a means to slow the inflammatory events responsible for tissue degeneration. Here we show that the natural polysaccharide alginate and particularly its sulfated derivatives have potent anti-oxidant, anti-inflammatory and anti-immunogenic properties in vitro...
June 23, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28643230/crosstalk-between-m2-macrophages-and-glioma-stem-cells
#4
Leora M Nusblat, Molly J Carroll, Charles M Roth
PURPOSE: Given its extremely poor prognosis, there is a pressing need for an improved understanding of the biology of glioblastoma multiforme (GBM), including the roles of tumor subpopulations that may contribute to their growth rate and therapy resistance. The most malignant phenotypes of GBM have been ascribed to the presence of subpopulations of cancer stem cells (CSCs), which are resistant to chemotherapeutic drugs and ionizing radiation and which promote invasiveness and metastasis...
June 22, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28643135/preoperative-tumor-restaging-and-resectability-assessment-of-gastric-cancers-after-chemotherapy-diagnostic-accuracy-of-mdct-using-new-staging-criteria
#5
Ijin Joo, Se Hyung Kim, Su Joa Ahn, Eun Sun Lee, Cheong-Il Shin, Hyuk-Joon Lee, Han Kwang Yang
PURPOSE: To evaluate the diagnostic performance of preoperative MDCT for tumor restaging and determination of resectability in gastric cancers after chemotherapy using new staging criteria. METHODS: This retrospective study was approved by our institutional review board and the requirement for informed consent was waived. Thirty-seven patients with initially unresectable gastric cancers who had received chemotherapy followed by surgery were included. Two independent radiologists reviewed preoperative MDCT images to determine the TNM staging and rate the overall likelihood of resectability using a 5-point scale (5: definitely unresectable, 1: definitely resectable)...
June 22, 2017: Abdominal Radiology
https://www.readbyqxmd.com/read/28642923/the-influence-of-particle-size-and-curing-conditions-on-testing-mineral-trioxide-aggregate-cement
#6
William Nguyen Ha, Bill Kahler, Laurence James Walsh
Objectives: To assess the effects on curing conditions (dry versus submerged curing) and particle size on the compressive strength (CS) and flexural strength (FS) of set MTA cement. Materials and methods: Two different Portland cements were created, P1 and P2, with P1 < P2 in particle size. These were then used to create two experimental MTA products, M1 and M2, with M1 < M2 in particle size. Particle size analysis was performed according to ISO 13320. The particle size at the 90th percentile (i.e. the larger particles) was P1: 15...
December 2016: Acta Biomaterialia Odontologica Scandinavica
https://www.readbyqxmd.com/read/28642908/methodologies-for-measuring-the-setting-times-of-mineral-trioxide-aggregate-and-portland-cement-products-used-in-dentistry
#7
William Nguyen Ha, Timothy Nicholson, Bill Kahler, Laurence James Walsh
Objective The current standard used to measure setting time for Mineral Trioxide Aggregate (MTA) involves indentation testing with arbitrary weights. This study compared indentation testing against rheological measurements and assessed the influences of particle size and the inclusion of bismuth oxide on the setting time of experimental MTA and Portland cement (PC). Material and methods Two PCs (P1 and P2) of different particle sizes were produced using the same clinker. From these two PCs, two experimental MTAs (M1 and M2) were created with the addition of bismuth oxide...
December 2016: Acta Biomaterialia Odontologica Scandinavica
https://www.readbyqxmd.com/read/28642762/arbuscular-mycorrhiza-augments-arsenic-tolerance-in-wheat-triticum-aestivum-l-by-strengthening-antioxidant-defense-system-and-thiol-metabolism
#8
Surbhi Sharma, Garima Anand, Neeraja Singh, Rupam Kapoor
Arbuscular mycorrhiza (AM) can help plants to tolerate arsenic (As) toxicity. However, plant responses are found to vary with the host plant and the AM fungal species. The present study compares the efficacy of two AM fungi Rhizoglomus intraradices (M1) and Glomus etunicatum (M2) in amelioration of As stress in wheat (Triticum aestivum L. var. HD-2967). Mycorrhizal (M) and non-mycorrhizal (NM) wheat plants were subjected to four levels of As (0, 25, 50, and 100 mg As kg(-1) soil). Although As additions had variable effects on the percentage of root colonized by the two fungal inoculants, each mycobiont conferred benefits to the host plant...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28642697/targeting-microglial-activation-states-as-a-therapeutic-avenue-in-parkinson-s-disease
#9
REVIEW
Sudhakar R Subramaniam, Howard J Federoff
Parkinson's disease (PD) is a chronic and progressive disorder characterized neuropathologically by loss of dopamine neurons in the substantia nigra, intracellular proteinaceous inclusions, reduction of dopaminergic terminals in the striatum, and increased neuroinflammatory cells. The consequent reduction of dopamine in the basal ganglia results in the classical parkinsonian motor phenotype. A growing body of evidence suggest that neuroinflammation mediated by microglia, the resident macrophage-like immune cells in the brain, play a contributory role in PD pathogenesis...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28642237/mediator-1-is-atherosclerosis-protective-by-regulating-macrophage-polarization
#10
Liang Bai, Zhao Li, Qianwei Li, Hua Guan, Sihai Zhao, Ruihan Liu, Rong Wang, Jin Zhang, Yuzhi Jia, Jianglin Fan, Nanping Wang, Janardan K Reddy, John Y-J Shyy, Enqi Liu
OBJECTIVE: MED1 (mediator 1) interacts with transcription factors to regulate transcriptional machinery. The role of MED1 in macrophage biology and the relevant disease state remains to be investigated. APPROACH AND RESULTS: To study the molecular mechanism by which MED1 regulates the M1/M2 phenotype switch of macrophage and the effect on atherosclerosis, we generated MED1/apolipoprotein E (ApoE) double-deficient (MED1(ΔMac)/ApoE(-)(/-)) mice and found that atherosclerosis was greater in MED1(ΔMac)/ApoE(-/-) mice than in MED1(fl/fl)/ApoE(-/-) littermates...
June 22, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28642037/testosterone-regulates-3t3-l1pre-adipocyte-differentiation-and-epididymal-fat-accumulation-in-mice-through-modulating-macrophage-polarization
#11
Xiaojiao Ren, Xiaojian Fu, Xinhua Zhang, Shiqiang Chen, Shuguang Huang, Lun Yao, Guoquan Liu
Low testosterone levels are strongly related to obesity in males. The balance between the classically M1 and alternatively M2 polarized macrophages also plays a critical role in obesity. It is not clear whether testosterone regulates macrophage polarization and then affects adipocyte differentiation. In this report, we demonstrate that testosterone strengthens interleukin (IL) -4-induced M2 polarization and inhibits lipopolysaccharide (LPS) -induced M1 polarization, but has no direct effect on adipocyte differentiation...
June 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28641584/crotoxin-stimulates-an-m1-activation-profile-in-murine-macrophages-during-leishmania-amazonensis-infection
#12
L H S Farias, A P D Rodrigues, E C Coêlho, M F Santos, S C Sampaio, E O Silva
American tegumentary leishmaniasis is caused by different species of Leishmania. This protozoan employs several mechanisms to subvert the microbicidal activity of macrophages and, given the limited efficacy of current therapies, the development of alternative treatments is essential. Animal venoms are known to exhibit a variety of pharmacological activities, including antiparasitic effects. Crotoxin (CTX) is the main component of Crotalus durissus terrificus venom, and it has several biological effects. Nevertheless, there is no report of CTX activity during macrophage - Leishmania interactions...
June 23, 2017: Parasitology
https://www.readbyqxmd.com/read/28640790/microrna-155-deficiency-in-kupffer-cells-ameliorates-liver-ischemia-reperfusion-injury-in-mice
#13
Yakun Li, Dongxia Ma, Zhimin Wang, Jun Yang
BACKGROUND: MicroRNA-155 (miR-155) is known to be involved in autoimmune diseases, inflammation, and transplantation. However, its role in a warm hepatic ischemia-reperfusion (IR) model has not been fully elucidated. METHODS: Partial hepatic IR was performed in wild-type and miR-155-deficient mice treated with or without GdCl3, and then the serum transaminase concentration and histology were analyzed. Kupffer cells (KCs) were isolated from the liver after IR, and immunohistochemistry was used to evaluate activation and polarization...
July 2017: Transplantation
https://www.readbyqxmd.com/read/28640606/pharmacokinetics-of-mequindox-and-its-marker-residue-1-4-bisdesoxymequindox-in-swine-following-multiple-oral-gavage-and-intramuscular-administration-an-experimental-study-coupled-with-population-physiologically-based-pharmacokinetic-modeling
#14
Dongping Zeng, Zhoumeng Lin, Binghu Fang, Miao Li, Ronette Gehring, Jim E Riviere, ZhenLing Zeng
Mequindox (MEQ) is a quinoxaline-N,N-dioxide antibiotic used in food-producing animals. MEQ residue in animal-derived foods is a food safety concern. The tissue distribution of MEQ and its marker residue 1,4-bisdesoxymequindox (M1) was determined in swine following oral gavage or intramuscular injection twice daily for 3 days. The experimental data were used to construct a flow-limited physiologically based pharmacokinetic (PBPK) model. The model predictions correlated with available data well. Monte Carlo analysis showed that the times needed for M1 concentrations to fall below limit of detection (5 µg/kg) in liver for the 99th percentile of the population were 27 and 34 days after oral gavage and intramuscular administration twice daily for 3 days, respectively...
June 22, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28638339/nutritional-and-pharmacological-strategies-to-regulate-microglial-polarization-in-cognitive-aging-and-alzheimer-s-disease
#15
REVIEW
Emiliano Peña-Altamira, Sabrina Petralla, Francesca Massenzio, Marco Virgili, Maria L Bolognesi, Barbara Monti
The study of microglia, the immune cells of the brain, has experienced a renaissance after the discovery of microglia polarization. In fact, the concept that activated microglia can shift into the M1 pro-inflammatory or M2 neuroprotective phenotypes, depending on brain microenvironment, has completely changed the understanding of microglia in brain aging and neurodegenerative diseases. Microglia polarization is particularly important in aging since an increased inflammatory status of body compartments, including the brain, has been reported in elderly people...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28637652/gm-csf-and-m-csf-primed-m%C3%AF-s-present-similar-resolving-but-distinct-inflammatory-lipid-mediator-signatures
#16
Ana Lukic, Pia Larssen, Alexander Fauland, Bengt Samuelsson, Craig E Wheelock, Susanne Gabrielsson, Olof Radmark
M1 and M2 activated Mϕs have different roles in inflammation. Because pathogens may first encounter resting cells, we investigated lipid mediator profiles prior to full activation. Human monocytes were differentiated with granulocyte Mϕ colony-stimulating factor (GM-CSF) or Mϕ colony-stimulating factor (M-CSF), which are known to prime toward M1 or M2 phenotypes, respectively. Lipid mediators released during resting conditions and produced in response to bacterial stimuli (LPS/N-formylmethionyl-leucyl-phenylalanine or peptidoglycan) were quantified by liquid chromatography-mass spectrometry...
June 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28637012/infiltrating-macrophages-in-diabetic-nephropathy-promote-podocytes-apoptosis-via-tnf-%C3%AE-ros-p38mapk-pathway
#17
Yinfeng Guo, Zhixia Song, Min Zhou, Ying Yang, Yu Zhao, Bicheng Liu, Xiaoliang Zhang
Macrophage infiltration has been linked to the pathogenesis of diabetic nephropathy (DN). However, how infiltrating macrophages affect the progression of DN is unknown. Although infiltrating macrophages produce pro-inflammatory mediators and induce apoptosis in a variety of target cells, there are no studies in podocytes. Therefore, we tested the contribution of macrophages to podocytes apoptosis in DN. in vivo experiments showed that apoptosis in podocytes was increased in streptozocin (STZ)-induced diabetic rats compared with control rats and that this apoptosis was accompanied by increased macrophages infiltration in the kidney...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28634882/gingipain-of-porphyromonas-gingivalis-manipulates-m1-macrophage-polarization-through-c5a-pathway
#18
Yubo Hou, Haiyan Yu, Xinchan Liu, Gege Li, Jiahui Pan, Changyu Zheng, Weixian Yu
Gingipains secreted by Porphyromonas gingivalis (P. gingivalis, Pg) play an important role in maintaining macrophage infiltrating. And, this study is to evaluate effects of gingipain on M1 macrophage polarization after exposure to Porphyromonas gingivalis (P. gingivalis, Pg) and if these effects are through complement component 5a (C5a) pathway. Mouse RAW264.7 macrophages were exposed to gingipain extracts, Escherichia coli lipopolysaccharides (Ec-LPS), Pg-LPS with or without the C5aR antagonist: PMX-53 for 24 h...
June 20, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/28634420/characterization-of-the-proinflammatory-profile-of-synovial-fluid-derived-exosomes-of-patients-with-osteoarthritis
#19
Rossana Domenis, Rossella Zanutel, Federica Caponnetto, Barbara Toffoletto, Adriana Cifù, Cinzia Pistis, Paolo Di Benedetto, Araldo Causero, Massimo Pozzi, Fabrizio Bassini, Martina Fabris, Kayvan R Niazi, Patrick Soon-Shiong, Francesco Curcio
The purpose of this study is to characterize synovial fluid- (SF-) derived exosomes of patients with gonarthrosis comparing two methods of isolation and to investigate their immune regulatory properties. Extracellular vesicles (EVs) have been isolated from inflamed SF by polymer precipitation method and quantified by Exocet kit and by nanoparticle tracking analysis. Vesicles expressed all the specific exosomal markers by immunoblot and FACS. After isolation with Exoquick, a relevant contamination by immune complexes was detected, which required further magnetic bead-based purification to remove...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28634261/autophagy-gene-fip200-in-neural-progenitors-non-cell-autonomously-controls-differentiation-by-regulating-microglia
#20
Chenran Wang, Syn Yeo, Michael A Haas, Jun-Lin Guan
Recent studies have shown important roles for autophagy genes in the regulation of different tissue stem cells, including neural stem/progenitor cells (NSCs). However, little is known about whether autophagy can regulate NSCs through cell-extrinsic mechanisms. Here, we show that deletion of an essential autophagy gene, FIP200, in NSCs increased expression of Ccl5 and Cxcl10 in a p53-independent manner, mediating increased infiltration of microglia into the subventricular zone of both FIP200hGFAP conditional knockout (cKO) and FIP200;p53hGFAP 2cKO mice...
June 20, 2017: Journal of Cell Biology
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