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Xiang Song, Yan Zhang, Li Zhang, Wengang Song, Lixin Shi
Hypoxia-associated metabolic reprogramming modulates the biological functions of many immune and non-immune cells, and affects immune response types and intensities. Adenosine and indoleamine 2,3-dioxygenase (IDO) are known immunosuppressors, and adenosine is a hypoxia-associated product. We investigated the impact of hypoxia on IDO production in dendritic cells (DCs). We found that hypoxia (1% O2 ) enhances IDO production in DCs, and this increase was dependent on the adenosine A3 receptor (A3R), but not A2aR or A2bR...
February 20, 2018: Oncotarget
Daniel B Rodrigues, Paulo S F Campos, Larry M Wolford, Jaqueline Ignácio, João R Gonçalves
PURPOSE: Maxillary segmentation involving interdental osteotomies can have an adverse effect on the interdental crestal bone and adjacent teeth. The purpose of the present study was to evaluate the effect of interdental osteotomies on surrounding osseous and dental structures, including adjacent teeth, using cone beam computed tomography (CBCT), in patients who underwent segmental maxillary osteotomies. PATIENTS AND METHODS: The present retrospective cohort study evaluated interdental osteotomy (IDO) sites between the lateral incisors and canines in patients treated with 3-piece Le Fort I osteotomies...
February 19, 2018: Journal of Oral and Maxillofacial Surgery
Julian A Marin-Acevedo, Bhagirathbhai Dholaria, Aixa E Soyano, Keith L Knutson, Saranya Chumsri, Yanyan Lou
Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent anti-tumor immune response. Immune checkpoint therapies act by blocking or stimulating these pathways and enhance the body's immunological activity against tumors. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1(PD-L1) are the most widely studied and recognized inhibitory checkpoint pathways...
March 15, 2018: Journal of Hematology & Oncology
Francisco S Barreto, Adriano J M Chaves Filho, Márcia C C R de Araújo, Manoel O de Moraes, Maria E A de Moraes, Michael Maes, David F de Lucena, Danielle S Macedo
Both depression and cancer are related to a dysregulation of inflammatory and immune pathways. Indeed, depression is associated with increased expression of interferon-γ, interleukin-1β, and tumor necrosis factor α (TNF-α). In contrast, reductions of the activity of major histocompatibility complex protein molecules - class I and class II and natural killer cells are also observed. Similarly, cancers present elevated levels of TNF-α, reduced major histocompatibility complex class I and II, and natural killer cells...
April 2018: Behavioural Pharmacology
Caroline Daly, Eve Griffin, Darren M Ashcroft, Roger T Webb, Ivan J Perry, Ella Arensman
Background: Intentional drug overdose (IDO) is the most common form of hospital-treated self-harm, yet no national study has systematically classified the range of drugs involved using a validated system. We aimed to determine the profile of patients engaging in overdose, to identify drugs frequently used and to quantify the contributions of multiple drug use and alcohol involvement. Methods: Between 2012 and 2014, the National Self-Harm Registry, Ireland recorded 18 329 presentations of non-fatal IDO to Irish emergency departments...
March 12, 2018: European Journal of Public Health
Toye Gabriel Olajide, Kayode Shuaib Aremu, Olaide T Esan, Adepeju Oluwatona Dosunmu, Mustapha Muhammad Raji
Background: Self-medication is a common habit in our country; Nigeria, especially among patients with otorhinolaryngological disorders. Medication when taken wrongly may bring dire consequences to the individual, such as masking developing diseases and may cause many other undesirable effects. The aim of this study was to determine the prevalence and to analyze topical ear drop self-medication practices among respondents attending the Ear, Nose, and Throat Clinic of Federal Teaching Hospital Ido Ekiti, Nigeria...
April 2018: Annals of African Medicine
Marco Mangiagalli, Guy Sarusi, Aleksei Kaleda, Maya Bar Dolev, Valentina Nardone, Vittoria Federica Vena, Ido Braslavsky, Marina Lotti, Marco Nardini
Ice Binding Proteins (IBPs) contribute to the survival of many living beings at sub-zero temperature by controlling the formation and growth of ice crystals. This work investigates the structural basis of the ice binding properties of EfcIBP, obtained from Antarctic bacteria. EfcIBP is endowed with a unique combination of thermal hysteresis (TH) and ice recrystallization inhibition (IRI) activity. The three-dimensional structure, solved at 0.84 Å resolution, shows that EfcIBP belongs to the IBP-1 fold family, and is organized in a right-handed β-solenoid with a triangular cross-section that forms three protein surfaces, named A, B and C faces...
March 13, 2018: FEBS Journal
Edwin Roger Parra, Pamela Villalobos, Jiexin Zhang, Carmen Behrens, Barbara Mino, Stephen Swisher, Boris Sepesi, Annika Weissferdt, Neda Kalhor, John Victor Heymach, Cesar Moran, Jianjun Zhang, Jack Lee, Jaime Rodriguez-Canales, Don Gibbons, Ignacio Ivan Wistuba
BACKGROUND: The understanding of immune checkpoint molecules' co-expression in non-small cell lung carcinoma (NSCLC) is important to potentially design combinatorial immunotherapy approaches. MATERIAL AND METHODS: We studied 225 formalin-fixed, paraffin-embedded tumor tissues from stage I-III NSCLCs-142 adenocarcinomas (ADCs) and 83 squamous cell carcinomas (SCCs)-placed in tissue microarrays. Nine immune checkpoint markers were evaluated; 4 (PD-L1, B7-H3, B7-H4, and IDO-1) expressed predominantly in malignant cells (MCs) and 5 (ICOS, VISTA, TIM3, LAG3, and OX40) expressed mostly in stromal tumor-associated inflammatory cells (TAICs)...
March 8, 2018: Journal of Thoracic Oncology
Noam Smorgick, Avital Mittler, Ido Ben-Ami, Ron Maymon, Zvi Vaknin, Moty Pansky
OBJECTIVE: To investigate whether women who were surgically treated for retained products of conception (RPOC) by either suction curettage or hysteroscopy are at risk for recurrent RPOC on their subsequent pregnancies. STUDY DESIGN: Retrospective analysis of 442 women surgically treated for RPOC following delivery or abortion by suction curettage (N = 63, 14.3%) or hysteroscopy (N = 379, 85.7%). Information on subsequent pregnancies and their outcomes was available for 161 (36...
March 5, 2018: European Journal of Obstetrics, Gynecology, and Reproductive Biology
Hidekazu Hachisu, Fumimaru Nakagawa, Yuko Hanado, Tetsuya Ido
Time scales consistently provide precise time stamps and time intervals by combining atomic frequency standards with a reliable local oscillator. Optical frequency standards, however, have not been applied to the generation of time scales, although they provide superb accuracy and stability these days. Here, by steering an oscillator frequency based on the intermittent operation of a87 Sr optical lattice clock, we realized an "optically steered" time scale TA(Sr) that was continuously generated for half a year...
March 9, 2018: Scientific Reports
Ariadne Androulidaki, Laurens Wachsmuth, Apostolos Polykratis, Manolis Pasparakis
Type 1 diabetes (T1D) is caused by the autoimmune destruction of the insulin-producing pancreatic beta cells. While the role of adaptive immunity has been extensively studied, the role of innate immune responses and particularly of Toll- like Receptor (TLR) signaling in T1D remains poorly understood. Here we show that myeloid cell-specific MyD88 deficiency considerably protected mice from the development of streptozotocin (STZ)-induced diabetes. The protective effect of MyD88 deficiency correlated with increased expression of the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) in pancreatic lymph nodes from STZ-treated mice and in bone marrow-derived dendritic cells (BMDC) stimulated with apoptotic cells...
2018: PloS One
Joshua Chiappelli, Francesca M Notarangelo, Ana Pocivavsek, Marian A R Thomas, Laura M Rowland, Robert Schwarcz, L Elliot Hong
Abnormalities in the kynurenine pathway (KP) of tryptophan degradation, leading to the dysfunction of neuroactive KP metabolites in the brain, have been implicated in the pathophysiology of schizophrenia (SZ). One plausible mechanism involves dysregulation of various pro-inflammatory cytokines associated with the disease, which affect indoleamine-2,3-dioxygenase (IDO), a key enzyme for tryptophan to kynurenine conversion. In order to test this hypothesis directly, we measured plasma levels of the major KP metabolites kynurenine and kynurenic acid (KYNA), as well as four major cytokines, in a sample of 106 SZ patients and 104 control participants...
February 27, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Jorge David Rojas Márquez, Yamile Ana, Ruth Eliana Baigorrí, Cinthia Carolina Stempin, Fabio Marcelo Cerban
The causative agent of Chagas' disease, Trypanosoma cruzi , affects approximately 10 million people living mainly in Latin America, with macrophages being one of the first cellular actors confronting the invasion during T. cruzi infection and their function depending on their proper activation and polarization into distinct M1 and M2 subtypes. Macrophage polarization is thought to be regulated not only by cytokines and growth factors but also by environmental signals. The metabolic checkpoint kinase mammalian target of rapamycin (mTOR)-mediated sensing of environmental and metabolic cues influences macrophage polarization in a complex and as of yet incompletely understood manner...
2018: Frontiers in Immunology
Sudeep Chenna Narendra, Jaya Prakash Chalise, Sophie Biggs, Ulrich Kalinke, Mattias Magnusson
Objective: CD4+ FoxP3+ CD25+ regulatory T-cells (Tregs ) are important for preventing tissue destruction. Here, we investigate the role of Tregs for protection against experimental arthritis by IFN-α. Methods: Arthritis was triggered by intra-articular injection of methylated bovine serum albumin (mBSA) in wild-type mice, Foxp3DTReGFP+/- mice [allowing selective depletion of Tregs by diphtheria toxin (DT)] and CD4-Cre+/- IFNA1R flox/flox mice (devoid of IFNAR signaling in T-cells) earlier immunized with mBSA, with or without treatment with IFN-α or the indoleamine 2,3-dioxygenase (IDO)-metabolite kynurenine...
2018: Frontiers in Immunology
Mark J Landau, Ido Badash, Christine Yin, Ram K Alluri, Ketan M Patel
BACKGROUND AND OBJECTIVES: Vascularized bone grafting after tumor resection can be an important component in the treatment of bony neoplasms of the upper extremity. The purpose of this study was to determine the outcomes of free vascularized fibula grafting (FVFG) in the treatment of upper extremity sarcomas. METHODS: A systematic review of the literature of FVFG used in the treatment of upper extremity sarcomas was performed. RESULTS: A total of 56 studies were included in final analysis...
March 7, 2018: Journal of Surgical Oncology
Rohini L Kadle, Salma A Abdou, Alvaro P Villarreal-Ponce, Marc A Soares, Darren L Sultan, Joshua A David, Jonathan Massie, William J Rifkin, Piul Rabbani, Daniel J Ceradini
Mesenchymal stem cells (MSCs) are known to both have powerful immunosuppressive properties and promote allograft tolerance. Determining the environmental oxygen tension and inflammatory conditions under which MSCs are optimally primed for this immunosuppressive function is essential to their utilization in promoting graft tolerance. Of particular interest is the mechanisms governing the interaction between MSCs and regulatory T cells (Tregs), which is relatively unknown. We performed our experiments utilizing rat bone marrow derived MSCs...
2018: PloS One
Theodoros Eleftheriadis, Georgios Pissas, Vassilios Liakopoulos, Ioannis Stefanidis
Indoleamine 2, 3-dioxygenase (IDO) suppresses T-cell function at least in part by altering cell metabolism. Hypoxia-inducible factor-1 (HIF-1) increases upon T-cell activation and alters cell metabolism favoring their differentiation to effector cells. The effect of IDO on HIF-1α expression and activity was evaluated. For this purpose, mixed lymphocyte reaction (MLR) was performed using the IDO inhibitor 1-DL-methyl-tryptophan and the p53 inhibitor pifithrin-α. L-tryptophan degradation and cell proliferation were assessed by enzyme-linked immunosorbent assay, whereas the expression of proteins of interest by western blotting...
February 2018: Iranian Journal of Allergy, Asthma, and Immunology
Richard P Nobrega, Eskinder Solomon, Julie Jenks, Tamsin Greenwell, Jeremy Ockrim
AIMS: To assess whether the urodynamic parameters of mean voided volume, peak detrusor overactivity (DO) pressure, bladder compliance, capacity, and volume at first detrusor overactivity during filling cystometry can predict a successful outcome at first stage tined lead placement (FSTLP). METHODS: Ninty-nine consecutive patients with urodynamically proven idiopathic detrusor overactivity (IDO) refractory to medical treatment and opting for Sacral Nerve Stimulation (SNS), were assessed pre and post FSTLP...
March 6, 2018: Neurourology and Urodynamics
Ido Azuri, Anna Hirsch, Anthony M Reilly, Alexandre Tkatchenko, Shai Kendler, Oded Hod, Leeor Kronik
We present a computational analysis of the terahertz spectra of the monoclinic and the orthorhombic polymorphs of 2,4,6-trinitrotoluene. Very good agreement with experimental data is found when using density functional theory that includes Tkatchenko-Scheffler pair-wise dispersion interactions. Furthermore, we show that for these polymorphs the theoretical results are only weakly affected by many-body dispersion contributions. The absence of dispersion interactions, however, causes sizable shifts in vibrational frequencies and directly affects the spatial character of the vibrational modes...
2018: Beilstein Journal of Organic Chemistry
Mazen S Albaghdadi, David M Dudzinski, Nicholas Giordano, Christopher Kabrhel, Brian Ghoshhajra, Michael R Jaff, Ido Weinberg, Aaron Baggish
BACKGROUND: Little data exist regarding the functional capacity of patients following acute pulmonary embolism. We sought to characterize the natural history of symptom burden, right ventricular (RV) structure and function, and exercise capacity among survivors of massive and submassive pulmonary embolism. METHODS AND RESULTS: Survivors of submassive or massive pulmonary embolism (n=20, age 57±13.3 years, 8/20 female) underwent clinical evaluation, transthoracic echocardiography, and cardiopulmonary exercise testing at 1 and 6 months following hospital discharge...
March 3, 2018: Journal of the American Heart Association
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