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https://www.readbyqxmd.com/read/29346764/sgk1-governs-the-reciprocal-development-of-th17-and-regulatory-t-cells
#1
Chuan Wu, Zuojia Chen, Sheng Xiao, Theresa Thalhamer, Asaf Madi, Timothy Han, Vijay Kuchroo
A balance between Th17 and regulatory T (Treg) cells is critical for immune homeostasis and tolerance. Our previous work has shown Serum- and glucocorticoid-induced kinase 1 (SGK1) is critical for the development and function of Th17 cells. Here, we show that SGK1 restrains the function of Treg cells and reciprocally regulates development of Th17/Treg balance. SGK1 deficiency leads to protection against autoimmunity and enhances self-tolerance by promoting Treg cell development and disarming Th17 cells. Treg cell-specific deletion of SGK1 results in enhanced Treg cell-suppressive function through preventing Foxo1 out of the nucleus, thereby promoting Foxp3 expression by binding to Foxp3 CNS1 region...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346621/assessing-polymyalgia-rheumatica-activity-when-c-reactive-protein-is-unavailable-or-uninterpretable
#2
Valérie Devauchelle-Pensec, Lea Saraux, Jean Marie Berthelot, Michel De Bandt, Divi Cornec, Dewi Guellec, Thierry Marhadour, Sandrine Jousse-Joulin, Maelenn Gouillou, Alain Saraux
Objective: The PMR activity score (PMR-AS) includes the CRP value, which may be lacking or invalid owing to anti-IL-6 therapy. Our objective was to develop alternatives to PMR-AS that do not require CRP. Methods: We used the Club Rhumatisme et Inflammation (CRI; 89 patients with PMR) and the Tolerance and Efficacy of tocilizumab iN pOlymyalgia Rheumatica (TENOR; 20 patients with recent-onset PMR naive to glucocorticoid who received three tocilizumab infusions, at weeks 0, 4 and 8, followed by prednisone from weeks 12 to 24) cohorts...
January 15, 2018: Rheumatology
https://www.readbyqxmd.com/read/29345162/genetic-defect-of-a-combined-17-%C3%AE-hydroxylase-17-20-lyase-deficiency-patient-with-adrenal-crisis
#3
Yunqiang Zhang, Xuyin Zhang, Yiqun Wang, Keqin Hua, Jingxin Ding
Combined 17 α-hydroxylase/17,20-lyase deficiency (17OHD) is a rare autosomal recessive disease that is a type of congenital adrenal hyperplasia, which results in hypertension, hypokalemia, sexual infantilism, primary amenorrhea in females (46,XX), or pseudohermaphroditism in males (46,XY). It is mainly caused by mutation in the CYP17A1 gene, which encodes a key enzyme in the steroidogenic pathway. However, these patients rarely experience adrenal crisis, due to abnormally high corticosterone levels. Here, we report a 17OHD patient who experienced clinical adrenal crisis on day 1 after gonadectomy...
January 18, 2018: Gynecological Endocrinology
https://www.readbyqxmd.com/read/29344906/mortality-in-patients-with-non-functioning-pituitary-adenoma
#4
REVIEW
Metaxia Tampourlou, Athanasios Fountas, Georgia Ntali, Niki Karavitaki
Non-functioning pituitary adenomas (NFA) are benign pituitary neoplasms not associated with clinical evidence of hormonal hypersecretion. A substantial number of patients with NFA have morbidities related to the tumor and possible recurrence(s), as well as to the treatments offered. Studies assessing the long-term mortality of patients with NFA are limited. Based on the published literature of the last two decades, overall, the standardized mortality ratios in this group suggest mortality higher than that of the general population with deaths attributed mainly to circulatory, respiratory and infectious causes...
January 17, 2018: Pituitary
https://www.readbyqxmd.com/read/29344793/the-role-of-bone-secreted-factors-in-burn-induced-muscle-cachexia
#5
REVIEW
Gordon L Klein
PURPOSE OF REVIEW: Burn injury results in resorptive bone loss, failure to make new bone, and muscle protein breakdown resulting in cachexia. The purpose of this review is to examine the relationship between bone loss and muscle atrophy in burn injury with a view to understanding the process at work and how it may apply to other conditions that have similar features. RECENT FINDINGS: We present data suggesting that the use of bisphosphonates in the first 10 days following the burn prevents not only the resorptive bone loss but also the muscle wasting...
January 17, 2018: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/29344777/giant-cell-arteritis-practical-pearls-and-updates
#6
REVIEW
Swati Pradeep, Jonathan H Smith
PURPOSE OF REVIEW: The purpose of this review is to summarize recent updates and distill practical points from the literature which can be applied to the care of patients with suspected and confirmed giant cell arteritis (GCA). RECENT FINDINGS: Contemporary thinking implicates a fundamental failure of T regulatory cell function in GCA pathophysiology, representing opportunity for novel therapeutic avenues. Tocilizumab has become the first Food and Drug Administration-approved treatment for GCA following demonstration of efficacy and safety in a phase 3 clinical trial...
January 17, 2018: Current Pain and Headache Reports
https://www.readbyqxmd.com/read/29344311/gilz-activin-a-as-a-novel-signaling-axis-orchestrating-mesenchymal-stem-cell-and-th17-cell-interplay
#7
Patricia Luz-Crawford, Gabriel Espinosa-Carrasco, Natacha Ipseiz, Rafael Contreras, Gautier Tejedor, Daniel A Medina, Ana-Maria Vega-Letter, Devi Ngo, Eric F Morand, Jérôme Pène, Javier Hernandez, Christian Jorgensen, Farida Djouad
Mesenchymal stem cells (MSC) are highly immunosuppressive cells able to reduce chronic inflammation through the active release of mediators. Recently, we showed that glucocorticoid-induced leucine zipper (Gilz) expression by MSC is involved in their therapeutic effect by promoting the generation of regulatory T cells. However, the mechanisms underlying this pivotal role of Gilz remain elusive. Methods and Results In this study, we have uncovered evidence that Gilz modulates the phenotype and function of Th1 and Th17 cells likely by upregulating the level of Activin A and NO2 secreted by MSC...
2018: Theranostics
https://www.readbyqxmd.com/read/29344177/characteristics-of-nosocomial-infection-and-its-effects-on-the-survival-of-chemotherapy-patients-with-advanced-non-small-cell-lung-cancer
#8
Lili Wang, Yan Li, Xia Zhang, Hongxia Li
The present study was planned to investigate the characteristics of nosocomial infection and its effects on the survival in advanced non-small cell lung cancer (NSCLC) patients. Retrospective analysis was performed for the 169 chemotherapy patients with NSCLC and nosocomial infection during hospitalization in Binzhou City Central Hospital from March, 2013 to January, 2015. In addition, 170 patients without nosocomial infection were also involved as a control group. The distribution of major drug resistance of Gram-negative (G-) and Gram-positive (G+) were analyzed...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344029/primary-adrenal-lymphoma-presenting-with-adrenal-failure-a-case-report-and-review-of-the-literature
#9
Fariba Karimi
Introduction: Primary adrenal lymphoma is rare, with a few cases reported in the literature. Most often it manifests as bilateral adrenal lesions and adrenal insufficiency is a common complication. Case Presentation: A 53-year-old male was referred with abdominal discomfort and darkening of the skin since 1 month prior to admission. His workups detected large bilateral adrenal masses. The patient was admitted due to hypotension, and was diagnosed with adrenal insufficiency...
October 2017: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29343424/igf1-mapk-erk-signaling-pathway-mediated-programming-alterations-of-adrenal-cortex-cell-proliferation-by-prenatal-caffeine-exposure-in-male-offspring-rats
#10
Guanghui Chen, Chao Yuan, Fangfang Duan, Yanyan Liu, Jinzhi Zhang, Zheng He, Hegui Huang, Chunjiang He, Hui Wang
Our previous study proposed a glucocorticoid-insulin-like growth factor 1 (GC-IGF1) axis programming mechanism for prenatal caffeine exposure (PCE)-induced adrenal developmental dysfunction. Here, we focused on PCE-induced cell proliferation changes of the adrenal cortex in male offspring rats before and after birth and clarified the intrauterine programming mechanism. On gestational day (GD) 20, the PCE group had an elevated serum corticosterone level reduced fetal bodyweight, maximum adrenal sectional area, and elevated adrenal corticosterone and aldosterone contents...
January 14, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29343273/inpp4b-promotes-cell-survival-via-sgk3-activation-in-npm1-mutated-leukemia
#11
Hongjun Jin, Liyuan Yang, Lu Wang, Zailin Yang, Qian Zhan, Yao Tao, Qin Zou, Yuting Tang, Jingrong Xian, Shuaishuai Zhang, Yipei Jing, Ling Zhang
BACKGROUND: Acute myeloid leukemia (AML) with mutated nucleophosmin (NPM1) has been recognized as a distinct leukemia entity in the 2016 World Health Organization (WHO) classification. The genetic events underlying oncogenesis in NPM1-mutated AML that is characterized by a normal karyotype remain unclear. Inositol polyphosphate 4-phosphatase type II (INPP4B), a new factor in the phosphoinositide-3 kinase (PI3K) pathway-associated cancers, has been recently found a clinically relevant role in AML...
January 17, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29343075/tocilizumab-in-giant-cell-arteritis-a-real-life-retrospective-study
#12
Gianfranco Vitiello, Carolina Orsi Battaglini, Giulia Carli, Anna Radice, Andrea Matucci, Alessandra Vultaggio, Catia Olianti, Paola Parronchi, Enrico Maggi, Daniele Cammelli
This study aims to evaluate (1) the efficacy and safety of tocilizumab (TCZ) as a steroid-sparing agent in patients with giant cell arteritis (GCA) and (2) the usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the follow-up and to detect disease activity. We retrospectively evaluated 12 patients with GCA treated with TCZ (8 mg/kg/mo). Pre- and posttherapy data about clinical signs and symptoms, laboratory results, FDG-PET imaging study, and the mean glucocorticoid (GC) dose were used to assess disease activity...
January 1, 2018: Angiology
https://www.readbyqxmd.com/read/29342499/efficacy-and-safety-of-cyclophosphamide-treatment-in-severe-juvenile-dermatomyositis-shown-by-marginal-structural-modelling
#13
Claire T Deakin, Raquel Campanilho-Marques, Stefania Simou, Elena Moraitis, Lucy R Wedderburn, Eleanor Pullenayegum, Clarissa A Pilkington
OBJECTIVE: In patients with severe or refractory juvenile dermatomyositis (JDM), second-line treatments may be required. Cyclophosphamide (CYC) is used to treat some connective tissue diseases, but evidence of efficacy in JDM is limited. This study aimed to describe clinical improvement in JDM patients treated with CYC and model efficacy of CYC compared to patients not treated with CYC. METHODS: Clinical data on skin, global and muscle disease were analyzed from patients recruited to the Juvenile Dermatomyositis Cohort and Biomarker Study...
January 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29342473/effectiveness-of-early-adalimumab-therapy-in-psoriatic-arthritis-patients-from-reuma-pt-early-psa
#14
Helena Santos, Mónica Eusébio, Joana Borges, Diana Gonçalves, Pedro Ávila-Ribeiro, Daniela Santos Faria, Carina Lopes, João Rovisco, Ana Águeda, Patrícia Nero, Paula Valente, Ana Rita Cravo, Maria José Santos
Objective To compare outcomes in psoriatic arthritis (PsA) patients initiating adalimumab (ADA), with short- and long-term disease duration and to evaluate the potential effect of concomitant conventional synthetic disease-modifying antirheumatic drugs (csDMARD) or glucocorticoids. Methods Analyses included adult PsA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt) between June 2008-June 2016 who received ADA for ≥3 months. Psoriatic Arthritis Response Criteria (PsARC) response, tender and swollen joint count, inflammatory parameters, patient (PtGA) and physician global assessment (PhGA), Disease Activity Score-28 joints (DAS28), and Health Assessment Questionnaire Disability Index (HAQ-DI) were compared between patients with <5 years of disease (early PsA) and those with ≥5 years of disease duration (late PsA)...
October 2017: Acta Reumatológica Portuguesa
https://www.readbyqxmd.com/read/29342458/glucocorticoids-modulate-th1-and-th2-responses-in-asthmatic-mouse-models-by-inhibition-of-notch1-signaling
#15
Chengping Hu, Zhifang Li, Juntao Feng, Yongjun Tang, Ling Qin, Xinyue Hu, Yan Zhang, Ruoxi He
BACKGROUND: Notch1 has been linked to the pathogenesis of asthma due to its contribution on Th1/Th2 imbalance. γ-Secretase inhibitor (GSI) acts as an effective blocker of Notch1 signaling. Glucocorticoids (GCs) are the most effective anti-inflammatory drugs for asthma. The present study investigated the involvement of the Notch1 pathway in the anti-inflammatory effect of GCs and its association with Th1/Th2 balance. METHODS: The asthma model was established in BALB/c mice by sensitization with ovalbumin (OVA)...
January 18, 2018: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/29341883/title-brain-region-specific-molecular-responses-to-maternal-separation-and-social-defeat-stress-in-mice
#16
Benjamin D Sachs, Ha L Tran, Emily Folse, Marc G Caron
The association between stress and mental illness has been well documented, but the molecular consequences of repeated exposure to stress have not been completely identified. The present study sought to elucidate the combinatorial effects of early life maternal separation stress and adult social defeat stress on alterations in signal transduction and gene expression that have been previously implicated in susceptibility to psychosocial stress. Molecular analyses were performed in the prelimbic/infralimbic cortex, amygdala, and nucleus accumbens, three brain regions that have been suggested to play critical roles in determining stress responses...
January 13, 2018: Neuroscience
https://www.readbyqxmd.com/read/29340736/risk-factors-for-early-infection-following-hemiarthroplasty-in-elderly-patients-with-a-femoral-neck-fracture
#17
Dirk Zajonz, Alexander Brand, Christian Lycke, Orkun Özkurtul, Jan Theopold, Ulrich J A Spiegl, Andreas Roth, Christoph Josten, Johannes K M Fakler
PURPOSE: Periprosthetic joint infections (PJI) after hemiarthroplasty for geriatric femoral neck fractures are a devastating complication that results in serious morbidity and increased mortality. Identifying risk factors associated with early infection after HA for hip fractures may offer an opportunity to address and prevent this complication in many patients. The aim of this study was to evaluate preoperative risk factors for early PJI after HA in hip fracture patients. METHODS: From January 2010 to December 2015, 312 femoral neck fractures (AO/OTA 31-B) in 305 patients were included in this single-center, retrospective study...
January 16, 2018: European Journal of Trauma and Emergency Surgery: Official Publication of the European Trauma Society
https://www.readbyqxmd.com/read/29339763/glucocorticoid-receptor-gr%C3%AE-regulates-glucocorticoid-induced-ocular-hypertension-in-mice
#18
Gaurang C Patel, Yang Liu, J Cameron Millar, Abbot F Clark
Prolonged glucocorticoid (GC) therapy can cause GC-induced ocular hypertension (OHT), which if left untreated progresses to iatrogenic glaucoma and permanent vision loss. The alternatively spliced isoform of glucocorticoid receptor GRβ acts as dominant negative regulator of GR activity, and it has been shown that overexpressing GRβ in trabecular meshwork (TM) cells inhibits GC-induced glaucomatous damage in TM cells. The purpose of this study was to use viral vectors to selectively overexpress the GRβ isoform in the TM of mouse eyes treated with GCs, to precisely dissect the role of GRβ in regulating steroid responsiveness...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339422/the-role-of-angiopoietin-like-protein-4-in-phenylephrine-induced-cardiomyocyte-hypertrophy
#19
Yu Sun, Yi Li, Chen Liu, Ruicong Xue, Bin Dong, Huiling Huang, Longyun Peng, Jun Liu, Yugang Dong
Angiopoietin-like protein 4 (ANGPTL4) is a multifunctional secreted protein that can be induced by fasting, hypoxia and glucocorticoids. ANGPTL4 has been associated with a variety of diseases, however, the role of ANGPTL4 in cardiac hypertrophy remains poorly understood. In our study, we aimed to explore the effect of ANGPTL4 on phenylephrine (PE)-induced cardiomyocyte hypertrophy. Our results showed that knockdown of ANGPTL4 expression significantly exacerbated cardiomyocyte hypertrophy, as demonstrated by increased hypertrophic marker expression, including ANP and cell surface area...
January 16, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29339091/an-energetic-view-of-stress-focus-on-mitochondria
#20
REVIEW
Martin Picard, Bruce S McEwen, Elissa Epel, Carmen Sandi
Energy is required to sustain life and enable stress adaptation. At the cellular level, energy is largely derived from mitochondria - unique multifunctional organelles with their own genome. Four main elements connect mitochondria to stress: 1) Energy is required at the molecular, (epi)genetic, cellular, organ, and systemic levels to sustain components of stress responses; 2) Glucocorticoids and other steroid hormones are produced and metabolized by mitochondria; 3) Reciprocally, mitochondria functionally respond to neuroendocrine and metabolic stress mediators; and 4) Experimentally manipulating mitochondrial functions alters physiological and behavioral responses to psychological stress...
January 12, 2018: Frontiers in Neuroendocrinology
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