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https://www.readbyqxmd.com/read/29778080/atrazine-xenobiotic-nuclear-receptor-interactions-induce-cardiac-inflammation-and-endoplasmic-reticulum-stress-in-quail-coturnix-coturnix-coturnix
#1
Xue-Nan Li, Yu-Zhu Zuo, Lei Qin, Wei Liu, Yan-Hua Li, Jin-Long Li
Atrazine (ATR) is one of the most extensively used herbicide that eventually leaches into groundwater and surface water from agricultural areas. Exposure to ATR does harm to the health of human and animals, especially the heart. However, ATR exposure caused cardiotoxicity in bird remains unclear. To evaluate ATR-exerted potential cardiotoxicity in heart, quail were exposed with 0, 50, 250, and 500 mg/kg BW/day ATR by gavage treatment for 45 days. Cardiac histopathological alternation was observed in ATR-induced quail...
May 9, 2018: Chemosphere
https://www.readbyqxmd.com/read/29777725/strain-related-differences-in-mouse-lung-gene-expression-over-a-two-year-period-of-inhalation-exposure-to-styrene-relevance-to-human-risk-assessment
#2
Melvin E Andersen, George Cruzan, Michael B Black, Salil N Pendse, Darol E Dodd, James S Bus, Satinder S Sarang, Marcy I Banton, Robbie Waites, Debra B Layko, Patrick D McMullen
Both CD-1 and C57BL/6 wildtype (C57BL/6-WT) mice show equivalent short-term lung toxicity from exposures to styrene, while long-term tumor responses are greater in CD-1 mice. We analyzed lung gene expression from styrene exposures lasting from 1-day to 2-years in male mice from these two strains, including a Cyp2f2(-/-) knockout (C57BL/6-KO) and a Cyp2F1/2A13/2B6 transgenic mouse (C57BL/6-TG). With short term exposures (1-day to 1-week), CD-1 and C57BL/6-WT mice had thousands of differentially expressed genes (DEGs), consistent with changes in pathways for cell proliferation, cellular lipid metabolism, DNA-replication and inflammation...
May 16, 2018: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29777230/serum-biomarkers-of-inflammation-and-adiposity-in-the-labs-cohort-associations-with-metabolic-disease-and-surgical-outcomes
#3
Robert W O'Rourke, Geoffrey S Johnson, Jonathan Q Purnell, Anita P Courcoulas, Gregory F Dakin, Luis Garcia, Marcelo Hinojosa, James E Mitchell, Alfons Pomp, Walter J Pories, Konstantinos Spaniolas, David R Flum, Abdus S Wahed, Bruce M Wolfe
BACKGROUND: The utility of serum biomarkers related to inflammation and adiposity as predictors of metabolic disease prevalence and outcomes after bariatric surgery are not well-defined. METHODS: Associations between pre- and post-operative serum levels of four biomarkers (C-reactive protein (CRP), cystatin C (CC), leptin, and ghrelin) with baseline measures of adiposity and metabolic disease prevalence (asthma, diabetes, sleep apnea), and weight loss and metabolic disease remission after bariatric surgery were studied in the Longitudinal Assessment of Bariatric Surgery (LABS) cohort...
May 17, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29776990/effect-of-2-psoriasis-treatments-on-vascular-inflammation-and-novel-inflammatory-cardiovascular-biomarkers-a-randomized-placebo-controlled-trial
#4
Nehal N Mehta, Daniel B Shin, Aditya A Joshi, Amit K Dey, April W Armstrong, Kristina Callis Duffin, Zelma Chiesa Fuxench, Charlotte L Harrington, Rebecca A Hubbard, Robert E Kalb, Alan Menter, Daniel J Rader, Muredach P Reilly, Eric L Simpson, Junko Takeshita, Drew A Torigian, Thomas J Werner, Andrea B Troxel, Stephen K Tyring, Suzette Baez Vanderbeek, Abby S Van Voorhees, Martin P Playford, Mark A Ahlman, Abass Alavi, Joel M Gelfand
BACKGROUND: Psoriasis is a chronic inflammatory disease associated with dyslipidemia, cardiovascular events, and mortality. We aimed to assess and compare the effect of treatment of moderate-to-severe psoriasis with adalimumab or phototherapy on vascular inflammation and cardiovascular biomarkers. METHODS AND RESULTS: Randomized, double-blind, trial of adalimumab, phototherapy, and placebo (1:1:1) for 12 weeks, with crossover to adalimumab for 52 weeks total. Outcomes included vascular inflammation by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography and biomarkers of inflammation, insulin resistance, and lipoproteins...
June 2018: Circulation. Cardiovascular Imaging
https://www.readbyqxmd.com/read/29776834/bet-bromodomain-ligands-probing-the-wpf-shelf-to-improve-brd4-bromodomain-affinity-and-metabolic-stability
#5
Laura E Jennings, Matthias Schiedel, David S Hewings, Sarah Picaud, Corentine M C Laurin, Paul A Bruno, Joseph P Bluck, Amy R Scorah, Larissa See, Jessica K Reynolds, Mustafa Moroglu, Ishna N Mistry, Amy Hicks, Pavel Guzanov, James Clayton, Charles N G Evans, Giulia Stazi, Philip C Biggin, Anna K Mapp, Ester M Hammond, Philip G Humphreys, Panagis Filippakopoulos, Stuart J Conway
Ligands for the bromodomain and extra-terminal domain (BET) family of bromodomains have shown promise as useful therapeutic agents for treating a range of cancers and inflammation. Here we report that our previously developed 3,5-dimethylisoxazole-based BET bromodomain ligand (OXFBD02) inhibits interactions of BRD4(1) with the RelA subunit of NF-κB, in addition to histone H4. This ligand shows a promising profile in a screen of the NCI-60 panel but was rapidly metabolised (t½  = 39.8 min). Structure-guided optimisation of compound properties led to the development of the 3-pyridyl-derived OXFBD04...
May 15, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29775748/microrna-204-5p-regulates-3t3-l1-preadipocyte-proliferation-apoptosis-and-differentiation
#6
Jingjing Du, Peiwen Zhang, Mailin Gan, Xue Zhao, Yan Xu, Qiang Li, Yanzhi Jiang, Guoqing Tang, Mingzhou Li, Jinyong Wang, Xuewei Li, Shunhua Zhang, Li Zhu
Obesity due to excessive lipid accumulation is closely associated with metabolic diseases such as type 2 diabetes, insulin resistance and inflammation. Therefore, a detailed understanding of the molecular mechanisms that underlie adipogenesis is crucial to develop treatments for diseases related to obesity. Here, we found that the microRNA-204-5p (miR-204-5p) was expressed at low levels in fat tissues from obese mice fed long-term with a high-fat diet (HFD). Overexpression or inhibition of miR-204-5p in vitro in 3T3-L1 preadipocytes significantly inhibited or promoted 3T3-L1 proliferation, respectively, an effect mediated by regulating cell proliferation factors...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29774069/a-large-switchable-optical-clearing-skull-window-for-cerebrovascular-imaging
#7
Chao Zhang, Wei Feng, Yanjie Zhao, Tingting Yu, Pengcheng Li, Tonghui Xu, Qingming Luo, Dan Zhu
Rationale: Intravital optical imaging is a significant method for investigating cerebrovascular structure and function. However, its imaging contrast and depth are limited by the turbid skull. Tissue optical clearing has a great potential for solving this problem. Our goal was to develop a transparent skull window, without performing a craniotomy, for use in assessing cerebrovascular structure and function. Methods: Skull optical clearing agents were topically applied to the skulls of mice to create a transparent window within 15 min...
2018: Theranostics
https://www.readbyqxmd.com/read/29773951/the-role-of-neuroinflammation-and-neurovascular-dysfunction-in-major-depressive-disorder
#8
REVIEW
Sang Won Jeon, Yong-Ku Kim
Although depression has generally been explained with monoamine theory, it is far more multifactorial, and therapies that address the disease's pathway have not been developed. In this context, an understanding of neuroinflammation and neurovascular dysfunction would enable a more comprehensive approach to depression. Inflammation is in a sense a type of allostatic load involving the immune, endocrine, and nervous systems. Neuroinflammation is involved in the pathophysiology of depression by increasing proinflammatory cytokines, activating the hypothalamus-pituitary-adrenal axis, increasing glucocorticoid resistance, and affecting serotonin synthesis and metabolism, neuronal apoptosis and neurogenesis, and neuroplasticity...
2018: Journal of Inflammation Research
https://www.readbyqxmd.com/read/29773170/iron-and-innate-antimicrobial-immunity-depriving-the-pathogen-defending-the-host
#9
REVIEW
Manfred Nairz, Stefanie Dichtl, Andrea Schroll, David Haschka, Piotr Tymoszuk, Igor Theurl, Günter Weiss
The acute-phase response is triggered by the presence of infectious agents and danger signals which indicate hazards for the integrity of the mammalian body. One central feature of this response is the sequestration of iron into storage compartments including macrophages. This limits the availability of this essential nutrient for circulating pathogens, a host defence strategy known as 'nutritional immunity'. Iron metabolism and the immune response are intimately linked. In infections, the availability of iron affects both the efficacy of antimicrobial immune pathways and pathogen proliferation...
July 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29773163/epicardial-adipose-tissue-may-mediate-deleterious-effects-of-obesity-and-inflammation-on-the-myocardium
#10
REVIEW
Milton Packer
Epicardial adipose tissue has unique properties that distinguish it from other depots of visceral fat. Rather than having distinct boundaries, the epicardium shares an unobstructed microcirculation with the underlying myocardium, and in healthy conditions, produces cytokines that nourish the heart. However, in chronic inflammatory disorders (especially those leading to heart failure with preserved ejection fraction), the epicardium becomes a site of deranged adipogenesis, leading to the secretion of proinflammatory adipokines that can cause atrial and ventricular fibrosis...
May 22, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29773067/in-silico-molecular-docking-and-adme-studies-of-1-3-4-thiadiazole-derivatives-in-relation-to-in-vitro-pon1-activity
#11
Belgin Sever, Kaan Kucukoglu, Hayrunnisa Nadaroglu, Mehlika Dilek Altintop
BACKGROUND: Paraoxonase 1 (PON1) is a paraoxonase, arylesterase and lactonase associated with protection of lipoproteins and cell membranes against oxidative modification. OBJECTIVE: Based on antioxidative properties of PON1 and widely usage of 1,3,4-thiadiazole derivatives in pharmaceutical, agricultural, and materials chemistry, herein we aimed to evaluate PON1 activator potentials of 1,3,4-thiadiazole based compounds. METHOD: 2-[[5-(2,4-Difluoro/dichlorophenylamino)-1,3,4-thiadiazol-2-yl]thio] acetophenone derivatives (1-18), previously synthesized by our research group, were in vitro evaluated for their activator effects on PON1 which was purified using ammonium sulfate precipitation (60-80%) and DEAE-Sephadex anion exchange chromatography...
May 17, 2018: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/29772682/the-association-of-dietary-fiber-intake-with-cardiometabolic-risk-in-four-countries-across-the-epidemiologic-transition
#12
Louise Lie, Laquita Brown, Terrence E Forrester, Jacob Plange-Rhule, Pascal Bovet, Estelle V Lambert, Brian T Layden, Amy Luke, Lara R Dugas
The greatest burden of cardiovascular disease is now carried by developing countries with cardiometabolic conditions such as metabolic syndrome, obesity and inflammation believed to be the driving force behind this epidemic. Dietary fiber is known to have protective effects against obesity, type 2 diabetes, cardiovascular disease and the metabolic syndrome. Considering the emerging prevalence of these cardiometabolic disease states across the epidemiologic transition, the objective of this study is to explore these associations of dietary fiber with cardiometabolic risk factors in four countries across the epidemiologic transition...
May 16, 2018: Nutrients
https://www.readbyqxmd.com/read/29772680/the-crosstalk-of-endoplasmic-reticulum-er-stress-pathways-with-nf-%C3%AE%C2%BAb-complex-mechanisms-relevant-for-cancer-inflammation-and-infection
#13
REVIEW
M Lienhard Schmitz, M Samer Shaban, B Vincent Albert, Anke Gökçen, Michael Kracht
Stressful conditions occuring during cancer, inflammation or infection activate adaptive responses that are controlled by the unfolded protein response (UPR) and the nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) signaling pathway. These systems can be triggered by chemical compounds but also by cytokines, toll-like receptor ligands, nucleic acids, lipids, bacteria and viruses. Despite representing unique signaling cascades, new data indicate that the UPR and NF-κB pathways converge within the nucleus through ten major transcription factors (TFs), namely activating transcription factor (ATF)4, ATF3, CCAAT/enhancer-binding protein (CEBP) homologous protein (CHOP), X-box-binding protein (XBP)1, ATF6α and the five NF-κB subunits...
May 16, 2018: Biomedicines
https://www.readbyqxmd.com/read/29772541/myeloid-heme-oxygenase-1-a-new-therapeutic-target-in-anti-inflammation
#14
Mingyi Zhao, Minghua Yang, Weitao Que, Lin Zhong, Masayuki Fujino, Xiao-Kang Li
An increasing amount of evidence reveals that an orchestrated interplay between myeloid subpopulations in the hematopoietic system plays a significant role in supporting normal functions of the immune system and facilitating homeostatic restoration upon exogenous or endogenous insults. Heme oxygenase-1 (HO-1), a microsomal enzyme discovered decades ago, can metabolize pro-oxidant heme into biliverdin, free iron, and carbon monoxide. This enzymatic reaction produces biological materials, contributing to major immunomodulatory effects...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29770504/black-pepper-piper-nigrum-essential-oil-demonstrates-tissue-remodeling-and-metabolism-modulating-potential-in-human-cells
#15
Xuesheng Han, Cody Beaumont, Damian Rodriguez, Tyler Bahr
Very few studies have investigated the biological activities of black pepper essential oil (BPEO) in human cells. Therefore, in the current study, we examined the biological activities of BPEO in cytokine-stimulated human dermal fibroblasts by analyzing the levels of 17 important protein biomarkers pertinent to inflammation and tissue remodeling. BPEO exhibited significant antiproliferative activity in these skin cells and significantly inhibited the production of Collagen I, Collagen III, and plasminogen activator inhibitor 1...
May 17, 2018: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29770231/cardiovascular-outcomes-of-pcsk9-inhibitors-with-special-emphasis-on-its-effect-beyond-ldl-cholesterol-lowering
#16
REVIEW
Dhrubajyoti Bandyopadhyay, Kumar Ashish, Adrija Hajra, Arshna Qureshi, Raktim K Ghosh
PCSK9 inhibitors, monoclonal antibodies, are novel antihypercholesterolemic drugs. FDA first approved them in July 2015. PCSK9 protein (692-amino acids) was discovered in 2003. It plays a major role in LDL receptor degradation and is a prominent modulator in low-density lipoprotein cholesterol (LDL-C) metabolism. PCSK9 inhibitors are monoclonal antibodies that target PCSK9 protein in liver and inhibiting this protein leads to drastically lowering harmful LDL-C level in the bloodstream. Despite widespread use of the statin, not all the high-risk patients were able to achieve targeted level of LDL-C...
2018: Journal of Lipids
https://www.readbyqxmd.com/read/29769661/circulating-mir-374a-5p-is-a-potential-modulator-of-the-inflammatory-process-in-obesity
#17
Ayo P Doumatey, William J He, Amadou Gaye, Lin Lei, Jie Zhou, Gary H Gibbons, Adebowale Adeyemo, Charles N Rotimi
Obese individuals without expected metabolic co-morbidities are referred to as metabolically healthy obese (MHO). The molecular mechanisms underlying this phenotype remain elusive. MicroRNAs may be involved in the MHO phenotype. To test this hypothesis, we screened 179 serum miRNAs in 20 African-American women (10 MHOs and 10 metabolically abnormal obese individuals -MAO). We identified 8 differentially expressed miRNAs (DEMs) with validation in an independent sample of 64 MHO and 34 MAO. Of the eight DEMs in the screening phase (p ≤ 0...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29768427/differential-effects-of-tnf-%C3%AE-and-il-1%C3%AE-on-the-control-of-metal-metabolism-and-cadmium-induced-cell-death-in-chronic-inflammation
#18
Paola Bonaventura, Aline Lamboux, Francis Albarède, Pierre Miossec
OBJECTIVE: Interleukin-1-beta (IL-1β) and tumour necrosis factor-alpha (TNF-α) are both monocyte-derived cytokines. Both cytokines have been previously described to exert a role in rheumatoid arthritis (RA) pathogenesis synergizing with other pro-inflammatory mediators, such as interleukin-17 (IL-17) on target cells, for the perpetuation of the inflammatory response (e.g. IL-6 production). In the context of experimental RA, Cd addition has an anti-proliferative and anti-inflammatory effect when associated to IL-17/TNF-α stimulation, due to its accumulation in synoviocytes...
2018: PloS One
https://www.readbyqxmd.com/read/29768212/mtor-senses-environmental-cues-to-shape-the-fibroblast-like-synoviocyte-response-to-inflammation
#19
Thomas Karonitsch, Richard K Kandasamy, Felix Kartnig, Barbara Herdy, Karolina Dalwigk, Birgit Niederreiter, Johannes Holinka, Florian Sevelda, Reinhard Windhager, Martin Bilban, Thomas Weichhart, Marcus Säemann, Thomas Pap, Günter Steiner, Josef S Smolen, Hans P Kiener, Giulio Superti-Furga
Accumulating evidence suggests that metabolic master regulators, including mTOR, regulate adaptive and innate immune responses. Resident mesenchymal tissue components are increasingly recognized as key effector cells in inflammation. Whether mTOR also controls the inflammatory response in fibroblasts is insufficiently studied. Here, we show that TNF signaling co-opts the mTOR pathway to shift synovial fibroblast (FLS) inflammation toward an IFN response. mTOR pathway activation is associated with decreased NF-κB-mediated gene expression (e...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29768198/myocardin-related-transcription-factor-a-promotes-recruitment-of-itga5-profibrotic-progenitors-during-obesity-induced-adipose-tissue-fibrosis
#20
Jean Z Lin, Nabil Rabhi, Stephen R Farmer
Adipose tissue fibrosis is associated with inflammation and insulin resistance in human obesity. In particular, visceral fat fibrosis is correlated with hyperlipidemia and ectopic fat accumulation. Myocardin-related transcription factor A (MRTFA) is an important coactivator that mediates the transcription of extracellular matrix and other fibrogenic genes. Here, we examine the role of MRTFA in the development of adipose tissue fibrosis and identify a signaling pathway that regulates the fate of vascular progenitors...
May 15, 2018: Cell Reports
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