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https://www.readbyqxmd.com/read/29351550/differential-actions-of-ppar-%C3%AE-and-ppar-%C3%AE-%C3%AE-on-beige-adipocyte-formation-a-study-in-the-subcutaneous-white-adipose-tissue-of-obese-male-mice
#1
Tamiris Lima Rachid, Flavia Maria Silva-Veiga, Francielle Graus-Nunes, Isabele Bringhenti, Carlos Alberto Mandarim-de-Lacerda, Vanessa Souza-Mello
BACKGROUND AND AIMS: Obesity compromises adipocyte physiology. PPARs are essential to adipocyte plasticity, but its isolated role in the browning phenomenon is not clear. This study aimed to examine whether activation of PPAR-α or PPAR-β/δ could induce beige cell depots in the subcutaneous white adipose tissue of diet-induced obese mice. MATERIAL AND METHODS: Sixty animals were randomly assigned to receive a control diet (C, 10% lipids) or a high-fat diet (HF, 50% lipids) for ten weeks...
2018: PloS One
https://www.readbyqxmd.com/read/29347939/prevalence-and-management-of-severe-asthma-in-primary-care-an-observational-cohort-study-in-sweden-pacehr
#2
Kjell Larsson, Björn Ställberg, Karin Lisspers, Gunilla Telg, Gunnar Johansson, Marcus Thuresson, Christer Janson
BACKGROUND: Severe and uncontrolled asthma is associated with increased risk of exacerbations and death. A substantial proportion of asthma patients have poor asthma control, and a concurrent COPD diagnosis often increases disease burden. The objective of the study was to describe the prevalence and managemant of severe asthma in a Swedish asthma popuöation. METHODS: In this observational cohort study, primary care medical records data (2006-2013) from 36 primary health care centers were linked to data from national mandatory Swedish health registries...
January 18, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29344432/wt1-peptide-vaccine-in-montanide-in-contrast-to-poly-iclc-is-able-to-induce-wt1-specific-immune-response-with-tcr-clonal-enrichment-in-myeloid-leukemia
#3
Hongtao Liu, Yuanyuan Zha, Noura Choudhury, Gregory Malnassy, Noreen Fulton, Margaret Green, Jae-Hyun Park, Yusuke Nakamura, Richard A Larson, Andres M Salazar, Olatoyosi Odenike, Thomas F Gajewski, Wendy Stock
Background: The optimal strategy for vaccination to induce CD8+ T cell responses against WT1 is not known. Methods: A pilot randomized study in HLA-A02+ patients to receive vaccination with WT1 in Montanide or in poly ICLC, a TLR3 agonist, to explore the novel immune adjuvant was conducted. Seven patients were randomized. Four patients received WT1 in Montanide, and three with WT1 in poly ICLC. Five patients were in morphologic remission and two had residual morphologic disease at the study entry...
2018: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29341930/activation-of-estrogen-receptor-beta-er%C3%AE-regulates-the-expression-of-n-cadherin-e-cadherin-and-%C3%AE-catenin-in-androgen-independent-prostate-cancer-cells
#4
Rafael de Souza Silva, Ana Paola G Lombardi, Deborah Simão de Souza, Carolina M Vicente, Catarina S Porto
The aim of the present study was to investigate the impact of the activation of estrogen receptors on expression and localization of N-cadherin, E-cadherin and non-phosphorylated β-catenin in androgen-independent prostate cancer cells (PC-3 and DU-145) and in human post pubertal prostate epithelial cells (PNT1A). Expression of N-cadherin was detected in PNT1A and PC-3 cells, but not in DU-145 cells. E-cadherin was detected only in DU-145 cells and β-catenin was detected in all cells studied. N-cadherin and β-catenin were located preferentially in the cellular membrane of PNT1A cells and in the cytoplasm of PC-3 cells...
January 13, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29339522/effect-of-beta-agonists-on-lam-progression-and-treatment
#5
Kang Le, Wendy K Steagall, Mario Stylianou, Gustavo Pacheco-Rodriguez, Thomas N Darling, Martha Vaughan, Joel Moss
Lymphangioleiomyomatosis (LAM), a rare disease of women, is associated with cystic lung destruction resulting from the proliferation of abnormal smooth muscle-like LAM cells with mutations in the tuberous sclerosis complex (TSC) genes TSC1 and/or TSC2 The mutant genes and encoded proteins are responsible for activation of the mechanistic target of rapamycin (mTOR), which is inhibited by sirolimus (rapamycin), a drug used to treat LAM. Patients who have LAM may also be treated with bronchodilators for asthma-like symptoms due to LAM...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29327658/immunohistochemical-analysis-of-il-1-receptor-1-in-the-discs-of-patients-with-temporomandibular-joint-dysfunction
#6
Luis Eduardo Almeida, Adam Sorenson, Kyle Hresko, Seth Butcher, Rosalia Leonardi, Carla Loreto, Jose Bosio, Lobat Tayebi, Andrea Doetzer
Objective Temporomandibular joint dysfunction (TMD) may affect a patient's quality of life, and one of the etiologies can be anterior disc displacement with reduction (ADDwR) and anterior disc displacement without reduction (ADDWoR). Interleukin 1 Receptor 1 (IL-1R1) is a membrane receptor that plays an important role on initiating immune and inflammatory response by binding the agonists ligands of IL-1 alpha and IL-1 beta. Therefore, the aim of this study was to evaluate, through immunohistochemical analysis, the association of IL-1R1 with TMD...
January 12, 2018: Cranio: the Journal of Craniomandibular Practice
https://www.readbyqxmd.com/read/29327400/a-vitamin-b12-conjugate-of-exendin-4-improves-glucose-tolerance-without-associated-nausea-or-hypophagia-in-rodents
#7
Elizabeth G Mietlicki-Baase, Claudia G Liberini, Jayme L Workinger, Ron L Bonaccorso, Tito Borner, David J Reiner, Kieran Koch-Laskowski, Lauren E McGrath, Rinzin Lhamo, Lauren M Stein, Bart C De Jonghe, George G Holz, Christian L Roth, Robert P Doyle, Matthew R Hayes
AIMS: While pharmacological glucagon-like peptide-1 receptor (GLP-1R) agonists are FDA-approved for treating type 2 diabetes mellitus (T2DM) and obesity, a major side effect is nausea/malaise. We recently developed a conjugate of vitamin B12 bound to the GLP-1R agonist exendin-4 (Ex4), which displays enhanced proteolytic stability and retention of GLP-1R agonism. Here, we evaluate whether the conjugate (B12-Ex4) can improve glucose tolerance without producing anorexia and malaise. MATERIALS AND METHODS: We evaluated the effects of systemic B12-Ex4 and unconjugated Ex4 on food intake and body weight change, oral glucose tolerance, and nausea/malaise in male rats, and on intraperitoneal glucose tolerance in mice...
January 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29317072/betacaryophyllene-a-phytocannabinoid-as-potential-therapeutic-modality-for-human-sepsis
#8
Angel Meza, Christian Lehmann
Sepsis is a clinical condition resulting from a dysregulated immune response to an infection that leads to organ dysfunction. Despite numerous efforts to optimize treatment, sepsis remains to be the main cause of death in most intensive care units. The endogenous cannabinoid system (ECS) plays an important role in inflammation. Cannabinoid receptor 2 (CB2R) activation is immunosuppressive, which might be beneficial during the hyper-inflammatory phase of sepsis. Beta-caryophyllene (BCP) is a non-psychoactive natural cannabinoid (phytocannabinoid) found in Cannabis sativa and in essential oils of spices and food plants, that acts as a selective agonist of CB2R...
January 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29301585/a-randomised-pragmatic-trial-of-corticosteroid-optimization-in-severe-asthma-using-a-composite-biomarker-algorithm-to-adjust-corticosteroid-dose-versus-standard-care-study-protocol-for-a-randomised-trial
#9
Catherine E Hanratty, John G Matthews, Joseph R Arron, David F Choy, Ian D Pavord, P Bradding, Christopher E Brightling, Rekha Chaudhuri, Douglas C Cowan, Ratko Djukanovic, Nicola Gallagher, Stephen J Fowler, Tim C Hardman, Tim Harrison, Cécile T Holweg, Peter H Howarth, James Lordan, Adel H Mansur, Andrew Menzies-Gow, Sofia Mosesova, Robert M Niven, Douglas S Robinson, Dominick E Shaw, Samantha Walker, Ashley Woodcock, Liam G Heaney
BACKGROUND: Patients with difficult-to-control asthma consume 50-60% of healthcare costs attributed to asthma and cost approximately five-times more than patients with mild stable disease. Recent evidence demonstrates that not all patients with asthma have a typical type 2 (T2)-driven eosinophilic inflammation. These asthmatics have been called 'T2-low asthma' and have a minimal response to corticosteroid therapy. Adjustment of corticosteroid treatment using sputum eosinophil counts from induced sputum has demonstrated reduced severe exacerbation rates and optimized corticosteroid dose...
January 4, 2018: Trials
https://www.readbyqxmd.com/read/29301581/activation-of-dopamine-d1-receptor-decreased-nlrp3-mediated-inflammation-in-intracerebral-hemorrhage-mice
#10
Tian Wang, Derek Nowrangi, Lingyan Yu, Tai Lu, Jiping Tang, Bing Han, Yuxin Ding, Fenghua Fu, John H Zhang
BACKGROUND: Inflammasomes are involved in diverse inflammatory diseases. Previous study reported that the neurotransmitter dopamine inhibited NLRP3 inflammasome activation via dopamine D1 receptor (DRD1). The present study aims to investigate the role of DRD1 on neuroinflammation in intracerebral hemorrhage (ICH) mice and the potential mechanism mediated by NLRP3 inhibition. METHODS: One hundred and six male CD-1 mice were subjected to intrastriatal injection of bacterial collagenase or PBS...
January 4, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29297151/liver-x-receptor-agonist-gw3965-regulates-synaptic-function-upon-amyloid-beta-exposure-in-hippocampal-neurons
#11
C Báez-Becerra, F Filipello, A Sandoval-Hernández, H Arboleda, G Arboleda
Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by beta-amyloid (Aβ) accumulation and neurofibrillary tangles formation in the brain which are associated to synaptic deficits and dementia. Liver X receptor (LXR) agonists have been demonstrated to revert of pathologic and cognitive defects in murine models of AD through the regulation of Apolipoprotein E, ATP-Binding Cassette A1 (ABCA1), by dampening neuroinflammation and also by reducing the levels of amyloid-β (Aβ) accumulation in the brain...
January 3, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29284659/a-targeted-rnai-screen-identifies-endocytic-trafficking-factors-that-control-glp-1-receptor-signaling-in-pancreatic-beta-cells
#12
Teresa Buenaventura, Nisha Kanda, Phoebe C Douzenis, Ben Jones, Stephen R Bloom, Pauline Chabosseau, Ivan R Corrêa, Domenico Bosco, Lorenzo Piemonti, Piero Marchetti, Paul R Johnson, Am James Shapiro, Guy A Rutter, Alejandra Tomas
The GLP-1 receptor (GLP-1R) is a key target for type 2 diabetes (T2D) treatment. Since endocytic trafficking of agonist-bound receptors is one of the most important routes for regulation of receptor signaling, a better understanding of this process may facilitate the development of new T2D therapeutic strategies. Here, we have screened 29 proteins with known functions in G protein-coupled receptor trafficking for their role in GLP-1R potentiation of insulin secretion in pancreatic beta cells. We identify five (clathrin, dynamin1, AP2, SNX27 and SNX1) that increase and four (HIP1, HIP14, GASP-1 and Nedd4) that decrease insulin secretion from murine insulinoma MIN6B1 cells in response to the GLP-1 analogue exendin-4...
December 28, 2017: Diabetes
https://www.readbyqxmd.com/read/29283978/review-hibernation-based-approaches-in-the-treatment-of-hemorrhagic-shock
#13
Andrea Wolf, Elizabeth R Lusczek, Gregory J Beilman
Hemorrhagic shock is the leading cause of preventable death after trauma. Hibernation-based treatment approaches have been of increasing interest for various biomedical applications. Due to apparent similarities in tissue perfusion and metabolic activity between severe blood loss and the hibernating state, hibernation-based approaches have also emerged for the treatment of hemorrhagic shock. Research has shown that hibernators are protected from shock-induced injury and inflammation. Utilizing the adaptive mechanisms that prevent injury in these animals may help alleviate the detrimental effects of hemorrhagic shock in non-hibernating species...
December 27, 2017: Shock
https://www.readbyqxmd.com/read/29283084/mirabegron-as-adjuvant-treatment-for-patients-with-interstitial-cystitis-bladder-pain-syndrome
#14
Michael Di Lena, Victoria Tolls, Kerri-Lynn Kelly, J Curtis Nickel
INTRODUCTION: Interstitial cystitis/bladder pain syndrome (IC/BPS) patients represent a heterogeneous group with pain and urinary storage symptoms and varying responses to current treatment options. The novel beta-3 agonist, mirabegron, has been shown to improve storage symptoms of patients with bladder overactivity; however, its effect on symptoms in the IC/BPS population has yet to be studied. METHODS: Patients diagnosed at a single IC centre with IC/BPS undergoing standard therapy were treated with additional daily mirabegron 25 mg and seen in followup post-treatment...
December 22, 2017: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/29279056/a-review-of-the-efficacy-and-safety-of-once-daily-tiotropium-respimat-2-5-micrograms-in-adults-and-adolescents-with-asthma
#15
Eli O Meltzer, William E Berger
BACKGROUND: Despite current guidelines, many patients with asthma remain symptomatic, particularly those intolerant of, unresponsive to, or uncontrolled by long-acting beta 2-agonists (LABAs). Tiotropium bromide, delivered through the Respimat soft-mist inhaler in 2 puffs of 1.25 micrograms each, is approved for the long-term, maintenance treatment of asthma in patients aged ≥6 years. OBJECTIVE: An overview of the use of once-daily tiotropium Respimat 2.5 micrograms in adults and adolescents with varying degrees of asthma severity...
January 6, 2018: Allergy and Asthma Proceedings:
https://www.readbyqxmd.com/read/29278993/adherence-to-gold-guidelines-in-the-inpatient-copd-population
#16
Melissa Lipari, Amber Lanae Smith, Pramodini B Kale-Pradhan, Sheila M Wilhelm
PURPOSE: The Global Initiative for Chronic Obstructive Lung Disease guidelines provide recommendations to manage chronic obstructive lung disease (COPD) exacerbations. This study assessed the management of inpatient COPD exacerbations at an urban teaching hospital. METHODS: A retrospective cohort analysis of adults admitted between December 2010 and August 2012 with a COPD exacerbation was conducted. Patient demographics, length of stay (LOS), Charlson comorbidity score, inpatient pulmonary medications, and 30-day readmission were collected...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/29277538/sexual-dimorphism-in-response-to-a-nrf2-inducer-in-a-model-for-pachyonychia-congenita
#17
Michelle L Kerns, Jill M C Hakim, Abigail Zieman, Rosemary G Lu, Pierre A Coulombe
Sex is an influential factor regarding pathophysiology and therapeutic response in human disease. Pachyonychia congenita (PC) is caused by mutations in keratin genes and typified by dystrophic lesions affecting nails, glands, oral mucosa, and palmar-plantar epidermis. Painful palmar-plantar keratoderma (PPK) severely impair mobility in PC. Mice genetically null for keratin 16 (Krt16), one of the genes mutated in PC, develop PC-like PPK. In male Krt16-/- mice, oxidative stress associated with impaired glutathione synthesis and NRF2-dependent gene expression precedes PPK onset, which can be prevented by topical sulforaphane (SF)-mediated activation of NRF2 (Kerns et al...
December 22, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29275517/sarsasapogenin-suppresses-a%C3%AE-overproduction-induced-by-high-glucose-in-ht-22-cells
#18
Meng-Ya Zhang, Yu Li, Shen-Yuan Yin, Li Kong, Xiao-Li Liu, Xiao-Xing Yin, Yao-Wu Liu
The aim of this study is to investigate effects and potential mechanisms of sarsasapogenin (Sar), an active component purified from Rhizoma Anemarrhenae, on high glucose-induced amyloid-beta (Aβ) peptide overproduction in HT-22 cells. HT-22 cells were divided into normal glucose; high glucose (HG); HG co-treated with low, middle, and high concentration of Sar (1, 5, 25 μmol/L); and peroxisome proliferator-activated receptor γ (PPARγ) agonist (10 μmol/L pioglitazone). After treatment for 24 h, protein expression of Aβ and β-site Aβ precursor protein cleaving enzyme 1 (BACE1) and activated PPARγ level were determined by Western blot; Aβ42 levels were also measured by using both immunofluorescence and ELISA methods...
December 23, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29273374/protective-effects-of-glutathione-on-oxidative-injury-induced-by-hydrogen-peroxide-in-intestinal-epithelial-cells
#19
Haitao Ren, Qinghe Meng, Natesh Yepuri, Xianjin Du, James Osei Sarpong, Robert N Cooney
BACKGROUND: Reactive oxygen species are increased in multiple gastrointestinal diseases and contribute to their pathogenesis. glutathione (GSH) is an antioxidant that helps to prevent reactive oxygen species-mediated mucosal damage. This study examines the mechanisms by which GSH attenuates hydrogen peroxide (H2O2)-induced injury in intestinal epithelial cells. METHODS: IEC-6 cells were cultured and treated with H2O2 ± GSH. Inflammation was measured by nuclear factor kappa-B (NF-κB) P65 expression, NF-κB nuclear translocation, iκBα phosphorylation, and interleukin 1 beta secretion...
February 2018: Journal of Surgical Research
https://www.readbyqxmd.com/read/29241811/syk-and-src-targeted-anti-inflammatory-activity-of-aripiprazole-an-atypical-antipsychotic
#20
Sulgi Yoo, Mi-Yeon Kim, Jae Youl Cho
Aripiprazole (ARP) is a partial agonist of dopamine D2 receptors that is commonly prescribed to treat schizophrenia and bipolar disorder. The anti-inflammatory effect of ARP was recently documented in a few studies, but its molecular mechanisms have not been fully elucidated. In this study, peptidoglycan (PGN)-treated macrophages (RAW264.7 cells), reporter gene assay, an overexpression strategy, immunoprecipitation, and immunoblotting analysis were employed to clarify the anti-inflammatory mechanism of ARP...
December 11, 2017: Biochemical Pharmacology
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