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https://www.readbyqxmd.com/read/28432362/succinate-supplementation-improves-metabolic-performance-of-mixed-glial-cell-cultures-with-mitochondrial-dysfunction
#1
Susan Giorgi-Coll, Ana I Amaral, Peter J A Hutchinson, Mark R Kotter, Keri L H Carpenter
Mitochondrial dysfunction, the inability to efficiently utilise metabolic fuels and oxygen, contributes to pathological changes following traumatic spinal cord or traumatic brain injury (TBI). In the present study, we tested the hypothesis that succinate supplementation can improve cellular energy state under metabolically stressed conditions in a robust, reductionist in vitro model of mitochondrial dysfunction in which primary mixed glial cultures (astrocytes, microglia and oligodendrocytes) were exposed to the mitochondrial complex I inhibitor rotenone...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28431280/interleukin-1-receptor-associated-kinase-1-is-a-potential-therapeutic-target-of-anti-inflammatory-therapy-for-systemic-lupus-erythematosus
#2
Mingfang Li, Datang Yu, Bing Ni, Fei Hao
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease and currently has no effective therapy. The genome-wide analyses indicate that interleukin-1 receptor associated kinase 1 (IRAK1) is associated with the susceptibility of SLE in humans. In the present study, we identified that IRAK1 was overexpressed and hyper-activated in splenic mononuclear cells from B6.MRL-Fas(lpr)/Nju (B6.lpr) mice and peripheral blood mononuclear cells (PBMCs) from SLE patients. Intraperitoneal treatment with a small molecular inhibitor of IRAK1 (IRAK1/4 inhibitor or IRAK-Inh) significantly mitigated inflammatory responses and renal injury in B6...
April 18, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28414116/the-largest-european-single-center-experience-300-laparoscopic-pancreatic-resections
#3
Safi Dokmak, Fadhel Samir Ftériche, Béatrice Aussilhou, Philippe Lévy, Philippe Ruszniewski, Jérome Cros, Marie Pierre Vullierme, Linda Khoy Ear, Jacques Belghiti, Alain Sauvanet
BACKGROUND: Although laparoscopic pancreatic resection (LPR) has become a routine, large single center series are still lacking. Our aim was to analyze the results of a large European single center series of LPR. STUDY DESIGN: Between January 2008 and September 2015, 300 LPR were performed and studied prospectively including 165 (55%) distal pancreatectomies, 68 (23%) pancreatoduodenectomies (PD), 30 (10%) enucleations, 35 (11%) central pancreatectomies and 2 (1%) total pancreatectomies...
April 13, 2017: Journal of the American College of Surgeons
https://www.readbyqxmd.com/read/28401431/sustained-immunosuppression-alters-olfactory-function-in-the-mrl-model-of-cns-lupus
#4
Minesh Kapadia, Hui Zhao, Donglai Ma, Boris Sakic
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is frequently accompanied by diverse neuropsychiatric manifestations. An increased frequency of olfactory deficits has been recently reported as another marker of CNS involvement in SLE patients. Similarly, we observed that spontaneous development of lupus-like disease in MRL/lpr mice is accompanied by altered olfaction-related behaviors. However, it remained unclear whether the behavioral deficits are due to systemic autoimmunity, or the distinct genetic make-up...
April 11, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28396669/basophil-activation-dependent-autoantibody-and-interleukin-17-production-exacerbate-systemic-lupus-erythematosus
#5
Qingjun Pan, Li Gong, Haiyan Xiao, Yongmin Feng, Lu Li, Zhenzhen Deng, Ling Ye, Jian Zheng, Carol A Dickerson, Lin Ye, Ning An, Chen Yang, Hua-Feng Liu
OBJECTIVE: Autoantibody and inflammatory cytokines play crucial roles in the development of systemic lupus erythematosus (SLE); however, the regulation of their production warrants further investigation. This study aimed to investigate the role of basophil activation in the development of SLE based on studies in patients with SLE and spontaneous lupus-prone MRL-lpr/lpr mice. METHODS: The phenotypes of peripheral basophils and the production of autoantibody and interleukin (IL)-17 in patients with SLE were determined by flow cytometry and enzyme-linked immunosorbent assay, and also their correlations were investigated by statistical analysis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28393618/regulatory-b-cells-are-functionally-impaired-in-patients-having-hemophilia-a-with-inhibitors
#6
Mohamed-Rachid Boulassel, Maryam Al-Ghonimi, Badriya Al-Balushi, Amal Al-Naamani, Zahra Al-Qarni, Yasser Wali, Mohamed Elshinawy, Maryam Al-Shezawi, Hamad Khan, Hanan Nazir, Doaa Khater, Anil Pathare, Salam Al-Kindi
Development of inhibitors remains a major clinical complication in patients with hemophilia A receiving replacement therapy with factor VIII (FVIII). Understanding the immune mechanisms involved in the development of inhibitors can provide valuable information about pathways to human tolerance. Recent evidence indicates that B regulatory (Breg) cells play a pivotal role in controlling the production of antibodies (Abs) while promoting follicular T helper (Tfh) cells and monocytes, expressing the low-density lipoprotein receptor-related protein (LRP/CD91), which is involved in FVIII intake from the circulation...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28386087/delivery-of-enac-sirna-to-epithelial-cells-mediated-by-a-targeted-nanocomplex-a-therapeutic-strategy-for-cystic-fibrosis
#7
Maria D I Manunta, Aristides D Tagalakis, Martin Attwood, Ahmad M Aldossary, Josephine L Barnes, Mustafa M Munye, Alexander Weng, Robin J McAnulty, Stephen L Hart
The inhibition of ENaC may have therapeutic potential in CF airways by reducing sodium hyperabsorption, restoring lung epithelial surface fluid levels, airway hydration and mucociliary function. The challenge has been to deliver siRNA to the lung with sufficient efficacy for a sustained therapeutic effect. We have developed a self-assembling nanocomplex formulation for siRNA delivery to the airways that consists of a liposome (DOTMA/DOPE; L), an epithelial targeting peptide (P) and siRNA (R). LPR formulations were assessed for their ability to silence expression of the transcript of the gene encoding the α-subunit of the sodium channel ENaC in cell lines and primary epithelial cells, in submerged cultures or grown in air-liquid interface conditions...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28364096/-effects-of-dexamethasone-on-mrl-lpr-mice-with-systemic-lupus-erythematosus-complicated-with-cognitive-dysfunction
#8
Yuanyuan Wang, Jie Tang, Lin Shen, Jiangyan Li, Cheng Zha, Rui Wang, Kun Hu, Jin Xi, Jianrong Chang, Changhao Xie
To evaluate the effects of dexamethasone on systemic lupus erythematosus complicated with cognitive dysfunction.
 Methods: Ten wild type mice and 20 MRL/lpr mice were applied for the research. MRL/lpr mice were randomly assigned to a MRL/lpr group and a MRL/lpr + dexamethasone (1.5 mg/kg) group. Interleukin-6 (IL-6), IL-1β, and tumor necrosis factor alpha (TNF-α) in serum and hippocampus were detected. The protein phosphorylation levels of phosphoinositide 3-kinase (P-PI3K), protein kinase B (P-Akt), NF-kappa-B inhibitor alpha (P-IκBa) and nuclear transcription factor 
kappa-B p65 (P-NF-κB p65) were detected by Western blot, the level of P-NF-κB p65 also was detected by immunohistochemistry...
March 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28349581/tcf1-deficiency-ameliorates-autoimmune-lymphoproliferative-syndrome-alps-like-phenotypes-of-lpr-lpr-mice
#9
Xiaoxie Xu, Bolan Yu, Weibin Cai, Zhaofeng Huang
Autoimmune lymphoproliferative syndrome (ALPS) is an incurable disease, which is characterized by non-malignant autoimmune lymphoproliferation. TCF1 is a key effector in the canonical Wnt/β-catenin pathway, regulating the development, activation and function of T cells. In this study, we aimed to explore the potential role of TCF1 in the development of ALPS-like phenotypes of lpr/lpr mice. We acquired TCF1(-/-) lpr/lpr double mutant mice by crossing TCF1 deficiency mice with lpr/lpr mice. Splenocyte compositions, serum cytokines levels, anti-dsDNA antibody production and kidney pathology were examined in the TCF1(-/-) lpr/lpr mice...
March 28, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28344578/on-how-fas-apoptosis-independent-pathways-drive-t-cell-hyperproliferation-and-lymphadenopathy-in-lpr-mice
#10
Dimitrios Balomenos, Rahman Shokri, Lidia Daszkiewicz, Cristina Vázquez-Mateo, Carlos Martínez-A
Fas induces massive apoptosis in T cells after repeated in vitro T cell receptor (TCR) stimulation and is critical for lymphocyte homeostasis in Fas-deficient (lpr) mice. Although the in vitro Fas apoptotic mechanism has been defined, there is a large conceptual gap between this in vitro phenomenon and the pathway that leads to in vivo development of lymphadenopathy and autoimmunity. A striking abnormality in lpr mice is the excessive proliferation of CD4(+) and CD8(+) T cells, and more so of the double-negative TCR(+)CD4(-)CD8(-)B220(+) T cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28342978/a-new-benzenediamine-derivative-modulates-toll-like-receptors-induced-myeloid-dendritic-cells-activation-and-ameliorates-lupus-like-syndrome-in-mrllpr-lpr-mice
#11
Sheng Gao, Yongsheng Gong, Jianjian Ji, Linbo Yuan, Liping Han, Yimin Guo, Xiaofang Fan, Yayi Hou, Chunyan Hua
Modulators of the over-activation of myeloid dendritic cells (mDCs) by Toll-like receptors (TLRs) have an advantage in the treatment of systemic lupus erythematosus (SLE). This study was designed to evaluate the effects of FC-99, a novel benzenediamine derivative, on TLR-induced activation of mDCs, and to assess the efficacy of FC-99 in a murine model of SLE. In vitro, FC-99 inhibited the phenotypic (CD40 and MHC-II) and functional activation (IL-12 and CXCL10) of mDCs induced by TLR ligands. In vivo, MRLlpr/lpr mice displayed renal diseases associated with increased levels of proteinuria and immunoglobulin, which were ameliorated by FC-99...
May 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28337724/i-123-iomazenil-single-photon-emission-computed-tomography-for-detecting-loss-of-neuronal-integrity-in-patients-with-traumatic-brain-injury
#12
Kagari Abiko, Katsunori Ikoma, Tohru Shiga, Chietsugu Katoh, Kenji Hirata, Yuji Kuge, Kentaro Kobayashi, Nagara Tamaki
BACKGROUND: Traumatic brain injury (TBI) causes brain dysfunction in many patients. Using C-11 flumazenil (FMZ) positron emission tomography (PET), we have detected and reported the loss of neuronal integrity, leading to brain dysfunction in TBI patients. Similarly to FMZ PET, I-123 iomazenil (IMZ) single photon emission computed tomography (SPECT) is widely used to determine the distribution of the benzodiazepine receptor (BZR) in the brain cortex. The purpose of this study is to examine whether IMZ SPECT is as useful as FMZ PET for evaluating the loss of neuronal integrity in TBI patients...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28326123/relationship-between-depression-and-laryngopharyngeal-reflux
#13
Young-Hoon Joo, Youn-Su Song, Chi-Un Pae
This study investigated the relationship between depression, somatization, anxiety, personality, and laryngopharyngeal reflux (LPR). We prospectively analyzed 231 patients with symptoms with LPR using the laryngopharyngeal reflux symptom index and the reflux finding score. Seventy nine (34.2%) patients were diagnosed with LPR. A significant correlation was detected between the presence of LPR and total scores on the Patient Health Questionnaire-9 (5.6±5.3 vs. 4.0±4.6, p=0.017) and the 7-item Generalized Anxiety Disorder Scale (4...
March 2017: Psychiatry Investigation
https://www.readbyqxmd.com/read/28322077/enteral-nutrition-increases-interstitial-brain-glucose-levels-in-poor-grade-subarachnoid-hemorrhage-patients
#14
Mario Kofler, Alois J Schiefecker, Ronny Beer, Maxime Gaasch, Paul Rhomberg, John Stover, Bettina Pfausler, Claudius Thomé, Erich Schmutzhard, Raimund Helbok
Low brain tissue glucose levels after acute brain injury are associated with poor outcome. Whether enteral nutrition (EN) reliably increases cerebral glucose levels remains unclear. In this retrospective analysis of prospectively collected observational data, we investigate the effect of EN on brain metabolism in 17 poor-grade subarachnoid hemorrhage (SAH) patients undergoing cerebral microdialysis (CMD) monitoring. CMD-values were obtained hourly. A nutritional intervention was defined as the clinical routine administration of EN without supplemental parenteral nutrition...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28301594/daxx-plays-a-novel-role-in-t-cell-survival-but-is-dispensable-in-fas-induced-apoptosis
#15
Jinghe Li, Liangyue Qian, John P Dowling, Christine Curcione, Drishya Kurup, Jianke Zhang
Daxx was originally isolated as a Fas-binding protein. However, the in vivo function of Daxx in Fas-induced apoptosis has remained enigmatic. Fas plays an important role in homeostasis in the immune system. Fas gene mutations lead to autoimmune-lymphoproliferation (lpr) diseases characterized by hyperplasia of secondary lymphoid organs. It is well established that the FADD adaptor binds to Fas, and recruits/activates caspase 8. However, additional proteins including Daxx have also been indicated to associate with Fas...
2017: PloS One
https://www.readbyqxmd.com/read/28294985/effects-of-a-diet-based-weight-reducing-program-with-probiotic-supplementation-on-satiety-efficiency-eating-behaviour-traits-and-psychosocial-behaviours-in-obese-individuals
#16
Marina Sanchez, Christian Darimont, Shirin Panahi, Vicky Drapeau, André Marette, Valerie H Taylor, Jean Doré, Angelo Tremblay
This study evaluated the impact of probiotic supplementation (Lactobacillus rhamnosus CGMCC1.3724 (LPR)) on appetite sensations and eating behaviors in the context of a weight-reducing program. Obese men (n = 45) and women (n = 60) participated in a double-blind, randomized, placebo-controlled trial that included a 12-week weight loss period (Phase 1) based on moderate energy restriction, followed by 12 weeks of weight maintenance (Phase 2). During the two phases of the program, each subject consumed two capsules per day of either a placebo or a LPR formulation (10 mg of LPR equivalent to 1...
March 15, 2017: Nutrients
https://www.readbyqxmd.com/read/28291238/polymorphisms-of-5-htt-lpr-and-gn%C3%AE-3-825c-t-and-response-to-antidepressant-treatment-in-functional-dyspepsia-a-study-from-the-functional-dyspepsia-treatment-trial
#17
Yuri A Saito, G Richard Locke, Ann E Almazar, Ernest P Bouras, Colin W Howden, Brian E Lacy, John K DiBaise, Charlene M Prather, Bincy P Abraham, Hashem B El-Serag, Paul Moayyedi, Linda M Herrick, Lawrence A Szarka, Michael Camilleri, Frank A Hamilton, Cathy D Schleck, Katherine E Tilkes, Alan R Zinsmeister, Nicholas J Talley
OBJECTIVES: The Functional Dyspepsia Treatment Trial reported that amitriptyline (AMI) was associated with adequate relief of functional dyspepsia (FD) symptoms, but the pharmacogenetics of antidepressant response in FD are not known. GNβ3 825C>T CC genotype has been previously linked to FD and TT genotype to antidepressant response in depression. The ss genotype of the 5-HTT LPR variant of the serotonin transporter gene (SLC6A4) has been linked to selective serotonin reuptake inhibitor (SSRI) response...
March 14, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28278341/association-of-oral-antireflux-medication-with-laryngopharyngeal-reflux-and-nasal-resistance
#18
Elif Dagli, Alper Yüksel, Mesut Kaya, Kadriye Serife Ugur, Fatma Cansel Turkay
Importance: Laryngopharyngeal reflux (LPR) is thought to be a potential exacerbating factor in upper airway diseases. Objective: To describe the effect of pharmacologic therapy of laryngopharyngeal reflux on nasal resistance. Design, Setting, and Participants: Prospective observational study performed between August 30, 2014, and October 1, 2015, at a tertiary care academic center including 50 patients with Reflux Symptom Index higher than 13 and Reflux Finding Score higher than 7 and 50 controls with no history of LPR and nasal disease...
March 9, 2017: JAMA Otolaryngology—Head & Neck Surgery
https://www.readbyqxmd.com/read/28278279/toll-like-receptor-9-suppresses-lupus-disease-in-fas-sufficient-mrl-mice
#19
Kevin M Nickerson, Yujuan Wang, Sheldon Bastacky, Mark J Shlomchik
Genetic deficiency in TLR9 accelerates pathogenesis in the spontaneous polygenic MRL.Faslpr murine model of systemic lupus erythematosus, despite the absence of anti-nucleosome autoantibodies. However, it could be argued that this result was dependent on Fas-deficiency rather than lupus-promoting genes in the MRL genetic background. Here we report the effects of TLR9 deficiency on autoimmune disease independent of the lpr mutation in Fas by characterizing Tlr9-/- and Tlr9+/+ mice on the Fas-intact MRL/+ genetic background...
2017: PloS One
https://www.readbyqxmd.com/read/28274306/-glycyrrhizinic-acid-modulates-the-immunity-of-mrl-lpr-mice-and-related-mechanism
#20
Yuanyuan Wang, Jixia Chai, Meiqun Sun, Wenxin He, Xiaodong Hu, Weiyan Zou, Huihui Li, Yang Lu, Changhao Xie
Objective To investigate the immunological effect of glycyrrhizic acid (GA) on MRL/lpr mice and its underlying mechanism. Methods The research included 10 wild type C57BL/6 mice and 40 MRL/lpr mice. MRL/lpr mice were randomly assigned to four groups: MRL/lpr control, MRL/lpr treated with dexamethasone (1.5 mg/kg), MRL/lpr treated with GA (20 mg/kg) and GA (40 mg/kg), 10 mice in each group. The serum levels of interleukin 4 (IL-4) and interferon-γ (IFN-γ) were tested by ELISA. The ratio of Th1/Th2 cell subsets in spleen was analyzed by flow cytometry...
March 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
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