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Dysregulation

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https://www.readbyqxmd.com/read/27936460/b-cells-present-skewed-profile-and-lose-the-function-of-supporting-t-cell-inflammation-after-roux-en-y-gastric-bypass
#1
Xiaojiang Dai, Weiguo Zhao, Junfang Zhan, Songhua Zeng, Dongzhi Ran, Hongbin Zhang, Zhigao Song, Ken H Song, Liangping Wu
Bariatric surgeries, including Roux-en-Y gastric bypass (RYGB) are currently the best treatment for obesity and obesity-related comorbidities, such as type 2 diabetes. However, the underlying mechanism of bariatric surgeries is not entirely understood. Further investigations are needed to improve the success rate and achieve sustained health benefits. Given that B cell dysregulation is a critical component of etiology in inflammatory diseases, whereas obesity and type 2 diabetes represent two major inflammatory disorders, we investigated the effect of RYGB on B cell inflammation...
December 6, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27936336/experiences-of-health-professionals-caring-for-people-presenting-to-the-emergency-department-after-taking-crystal-methamphetamine-ice
#2
Michelle Cleary, Debra Jackson, Cindy Woods, Rachel Kornhaber, Jan Sayers, Kim Usher
Globally, addiction to "ICE" (crystal methamphetamine) is increasing and presents emergency health care services personnel with a number of challenges. This paper reports the first of two major themes arising from a qualitative study investigating health professionals' experiences' managing people presenting to the Emergency Department (ED) after taking "ICE." The theme "Caring for people who use 'ICE' when presenting to EDs" comprises five subthemes. These are: (a) expecting the unexpected: "they're just off their heads"; (b) complexity of care: "underlying trauma and emotional dysregulation";...
December 9, 2016: Issues in Mental Health Nursing
https://www.readbyqxmd.com/read/27936104/mechanical-loading-attenuates-radiation-induced-bone-loss-in-bone-marrow-transplanted-mice
#3
Peter M Govey, Yue Zhang, Henry J Donahue
Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone's capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown...
2016: PloS One
https://www.readbyqxmd.com/read/27935981/sympathetic-hyperactivity-increased-tyrosine-hydroxylase-and-exaggerated-corpus-cavernosum-relaxations-associated-with-oxidative-stress-plays-a-major-role-in-the-penis-dysfunction-in-townes-sickle-cell-mouse
#4
Fábio H Silva, Mário A Claudino, Fabiano B Calmasini, Eduardo C Alexandre, Carla Franco-Penteado, Arthur L Burnett, Edson Antunes, Fernando F Costa
BACKGROUND: Sickle cell disease patients display priapism that may progress to erectile dysfunction. However, little is known about the pathophysiological alterations of corpus cavernosum in sickle cell disease. OBJECTIVE: Thus, this study aimed to evaluate the functional and molecular alterations of sympathetic machinery and nitric oxide-cyclic guanosine monophosphate signaling pathway in Townes transgenic sickle cell disease mice. METHODS: Concentration-response curves to contractile (phenylephrine) and relaxant agents (acetylcholine and sodium nitroprusside) were obtained in corpus cavernosum strips from sickle and C57BL/6 (control) mice...
2016: PloS One
https://www.readbyqxmd.com/read/27935957/intracellular-zn-ii-intoxication-leads-to-dysregulation-of-the-perr-regulon-resulting-in-heme-toxicity-in-bacillus-subtilis
#5
Pete Chandrangsu, John D Helmann
Transition metal ions (Zn(II), Cu(II)/(I), Fe(III)/(II), Mn(II)) are essential for life and participate in a wide range of biological functions. Cellular Zn(II) levels must be high enough to ensure that it can perform its essential roles. Yet, since Zn(II) binds to ligands with high avidity, excess Zn(II) can lead to protein mismetallation. The major targets of mismetallation, and the underlying causes of Zn(II) intoxication, are not well understood. Here, we use a forward genetic selection to identify targets of Zn(II) toxicity...
December 9, 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27935865/bronchial-airway-gene-expression-signatures-in-mouse-lung-squamous-cell-carcinoma-and-their-modulation-by-cancer-chemopreventive-agents
#6
Donghai Xiong, Jing Pan, Qi Zhang, Eva Szabo, Mark Steven Miller, Ronald A Lubet, Ming You, Yian Wang
Due to exposure to environmental toxicants, a "field cancerization" effect occurs in the lung resulting in the development of a field of initiated but morphologically normal appearing cells in the damaged epithelium of bronchial airways with dysregulated gene expression patterns. Using a mouse model of lung squamous cell carcinoma (SCC), we performed transcriptome sequencing (RNA-Seq) to profile bronchial airway gene expression and found activation of the PI3K and Myc signaling networks in cytologically normal bronchial airway epithelial cells of mice with preneopastic lung SCC lesions, which was reversed by treatment with the PI3K Inhibitor XL-147 and pioglitazone, respectively...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27935582/global-ischemia-induces-lysosomal-mediated-degradation-of-mtor-and-activation-of-autophagy-in-hippocampal-neurons-destined-to-die
#7
Jee-Yeon Hwang, Michael Gertner, Fabrizio Pontarelli, Brenda Court-Vazquez, Michael Vander Laan Bennett, Dimitry Ofengeim, Ruth Suzanne Zukin
The mammalian target of rapamycin (mTOR) is a key regulator of cell growth, autophagy, translation, and survival. Dysregulation of mTOR signaling is associated with cancer, diabetes, and autism. However, a role for mTOR signaling in neuronal death is not well delineated. Here we show that global ischemia triggers a transient increase in mTOR phosphorylation at S2448, whereas decreasing p-mTOR and functional activity in selectively vulnerable hippocampal CA1 neurons. The decrease in mTOR coincides with an increase in biochemical markers of autophagy, pS317-ULK-1, pS14-Beclin-1, and LC3-II, a decrease in the cargo adaptor p62, and an increase in autophagic flux, a functional readout of autophagy...
December 9, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27935134/strain-and-time-dependent-alterations-in-hepatic-iron-metabolism-in-a-murine-model-of-nonalcoholic-steatohepatitis
#8
Steven A Bloomer, Alicia K Olivier, Ottar M Bergmann, M Meleah Mathahs, Kimberly A Broadhurst, Hasan Hicsasmaz, Kyle E Brown
: Nonalcoholic steatohepatitis is a common liver disease that is often accompanied by dysregulated iron metabolism. The aim of the study was to test the hypothesis that aberrant iron metabolism in nonalcoholic steatohepatitis is modulated by genetic susceptibility to inflammation and oxidative stress. Hepatic histology and iron content were assessed in 3 inbred strains of mice (C57BL/6, BALB/c, and C3H/HeJ) fed an atherogenic diet (AD). Hepatic expression of genes relevant to iron metabolism, inflammation, and oxidative stress were quantitated by real-time reverse transcription-polymerase chain reaction...
December 2016: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/27934776/prediction-of-subjective-ratings-of-emotional-pictures-by-eeg-features
#9
Dennis J McFarland, Muhammad A Parvaz, William A Sarnacki, Rita Z Goldstein, Jonathan R Wolpaw
OBJECTIVE: Emotion dysregulation is an important aspect of many psychiatric disorders. Brain-computer interface (BCI) technology could be a powerful new approach to facilitating therapeutic self-regulation of emotions. One possible BCI method would be to provide stimulus-specific feedback based on subject-specific electroencephalographic (EEG) responses to emotion-eliciting stimuli. APPROACH: To assess the feasibility of this approach, we studied the relationships between emotional valence/arousal and three EEG features: amplitude of alpha activity over frontal cortex; amplitude of theta activity over frontal midline cortex; and the late positive potential over central and posterior mid-line areas...
December 9, 2016: Journal of Neural Engineering
https://www.readbyqxmd.com/read/27934635/metabolism-of-the-mek1-2-inhibitor-pimasertib-involves-a-novel-conjugation-with-phospho-ethanolamine-in-patients-with-solid-tumors
#10
Holger Scheible, Friedrich Kraetzer, Andreas Marx, Andreas Johne, Elmar Wimmer
Pimasertib (AS703026 or MSC1936369B) is a selective inhibitor of MEK1/2, the mitogen-activated protein kinase (MAPK) signaling pathway, which is often dysregulated in cancer cells. Pimasertib has shown potent preclinical anti tumor activity and its clinical activity is being investigated in various tumor types. In this phase I study, the disposition and biotransformation of (14)C-radiolabeled pimasertib was investigated in six patients with locally advanced or metastatic solid tumors (NCT 01713036). Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and radiodetection techniques were used to investigate the profiles and structures of metabolites in plasma, urine and feces after a single oral dose of (14)C-pimasertib...
December 1, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27933735/danazol-has-potential-to-cause-pkc-translocation-cell-cycle-dysregulation-and-apoptosis-in-breast-cancer-cells
#11
Suman Jyoti Deka, Ashalata Roy, Vibin Ramakrishnan, Debasis Manna, Vishal Trivedi
Danazol, the established clinical drug has given promising therapeutic results in a series of clinical trials with breast cancer patients. Danazol shares structural similarities with several known PKC agonists and fits well into the C1 domain. Danazol binds to the C1b domain of PKC with Kd of 5.64±1.27 μM. MD simulation studies further support that the PKC-Danazol molecular model is stable and showing minimum distortion to the structure during the simulation period. Immunofluorescence and western-blotting studies indicate that MDAMB-231 cells stimulated with danazol exhibit translocation of PKCα to the plasma membrane...
December 9, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27933366/deficits-in-autonomic-indices-of-emotion-regulation-and-reward-processing-associated-with-prescription-opioid-use-and-misuse
#12
Eric L Garland, Craig J Bryan, Yoshio Nakamura, Brett Froeliger, Matthew O Howard
RATIONALE: Prescription opioid misuse and high-dose opioid use may result in allostatic dysregulation of hedonic brain circuitry, leading to reduced emotion regulation capacity. In particular, opioid misuse may blunt the ability to experience and upregulate positive affect from natural rewards. OBJECTIVES: The purpose of this study was to examine associations between opioid use/misuse and autonomic indices of emotion regulation capability in a sample of chronic pain patients receiving prescription opioid pharmacotherapy...
December 8, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27933289/the-association-between-stress-measured-by-allostatic-load-score-and-physiologic-dysregulation-in-african-immigrants-the-africans-in-america-study
#13
Brianna A Bingham, Michelle T Duong, Madia Ricks, Lilian S Mabundo, Rafeal L Baker, Jean N Utumatwishima, Margaret Udahogora, David Berrigan, Anne E Sumner
INTRODUCTION: Allostatic load score (ALS) summarizes the physiological effect of stress on cardiovascular, metabolic and immune systems. As immigration is stressful, ALS could be affected. OBJECTIVE: Associations between age of immigration, reason for immigration, and unhealthy assimilation behavior and ALS were determined in 238 African immigrants to the United States (age 40 ± 10, mean ± SD, range 21-64 years). METHODS: ALS was calculated using 10 variables from three domains; cardiovascular (SBP, DBP, cholesterol, triglyceride, homocysteine), metabolic [BMI, A1C, albumin, estimated glomerular filtration rate (eGFR)], and immunological [high-sensitivity C-reactive protein (hsCRP)]...
2016: Frontiers in Public Health
https://www.readbyqxmd.com/read/27933176/pancreatic-%C3%AE-cell-hyperplasia-and-hyperglucagonemia-due-to-a-glucagon-receptor-splice-mutation
#14
Etienne Larger, Nicolai J Wewer Albrechtsen, Lars H Hansen, Richard W Gelling, Jacqueline Capeau, Carolyn F Deacon, Ole D Madsen, Fumiatsu Yakushiji, Pierre De Meyts, Jens J Holst, Erica Nishimura
: Glucagon stimulates hepatic glucose production by activating specific glucagon receptors in the liver, which in turn increase hepatic glycogenolysis as well as gluconeogenesis and ureagenesis from amino acids. Conversely, glucagon secretion is regulated by concentrations of glucose and amino acids. Disruption of glucagon signaling in rodents results in grossly elevated circulating glucagon levels but no hypoglycemia. Here, we describe a patient carrying a homozygous G to A substitution in the invariant AG dinucleotide found in a 3' mRNA splice junction of the glucagon receptor gene...
2016: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/27933062/no-role-for-mast-cells-in-obesity-related-metabolic-dysregulation
#15
Jindřich Chmelař, Antonios Chatzigeorgiou, Kyoung-Jin Chung, Marta Prucnal, David Voehringer, Axel Roers, Triantafyllos Chavakis
Obesity-related adipose tissue (AT) inflammation that promotes metabolic dysregulation is associated with increased AT mast cell numbers. Mast cells are potent inducers of inflammatory responses and could potentially contribute to obesity-induced AT inflammation and metabolic dysregulation. Conflicting findings were reported on obesity-related metabolic dysfunction in mast cell-deficient mice, thus creating a controversy that has not been resolved to date. Whereas traditional Kit hypomorphic mast cell-deficient strains featured reduced diet-induced obesity and diabetes, a Kit-independent model of mast cell deficiency, Cpa3(Cre/+) mice, displayed no alterations in obesity and insulin sensitivity...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27932613/type-1-reaction-in-leprosy-patients-corresponds-with-a-decrease-in-pro-resolving-and-an-increase-in-pro-inflammatory-lipid-mediators
#16
Carlos A M Silva, Kristofor Webb, Barbara G Andre, Maria Angela de Mello Marques, Fernanda Marques de Carvalho, Cristiana Santos de Macedo, Roberta Olmo Pinheiro, Euzenir Nunes Sarno, Maria Cristina Vidal Pessolani, John T Belisle
BACKGROUND: Type 1 reaction (T1R) is an acute Th1 inflammatory episode in leprosy patients. While immunological responses associated with T1R have been investigated, the corresponding metabolic responses that could contribute to T1R pathology have received little attention. METHODS: Metabolomics-based analyses of sera from T1R (n=7) and T1R-free (n=9) patients were conducted via liquid chromatography-mass spectrometry (LC-MS). Serum metabolites that significantly differed (p<0...
December 8, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27932477/moss-produced-glycosylation-optimized-human-factor-h-for-therapeutic-application-in-complement-disorders
#17
Stefan Michelfelder, Juliana Parsons, Lennard L Bohlender, Sebastian N W Hoernstein, Holger Niederkrüger, Andreas Busch, Nicola Krieghoff, Jonas Koch, Benjamin Fode, Andreas Schaaf, Thomas Frischmuth, Martin Pohl, Peter F Zipfel, Ralf Reski, Eva L Decker, Karsten Häffner
Genetic defects in complement regulatory proteins can lead to severe renal diseases, including atypical hemolytic uremic syndrome and C3 glomerulopathies, and age-related macular degeneration. The majority of the mutations found in patients with these diseases affect the glycoprotein complement factor H, the main regulator of the alternative pathway of complement activation. Therapeutic options are limited, and novel treatments, specifically those targeting alternative pathway activation, are highly desirable...
December 8, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27932276/the-why-and-how-of-amino-acid-analytics-in-cancer-diagnostics-and-therapy
#18
REVIEW
Friederike Manig, Konstantin Kuhne, Cläre von Neubeck, Uwe Schwarzenbolz, Zhanru Yu, Benedikt M Kessler, Jens Pietzsch, Leoni A Kunz-Schughart
Pathological alterations in cell functions are frequently accompanied by metabolic reprogramming including modifications in amino acid metabolism. Amino acid detection is thus integral to the diagnosis of many hereditary metabolic diseases. The development of malignant diseases as metabolic disorders comes along with a complex dysregulation of genetic and epigenetic factors affecting metabolic enzymes. Cancer cells might transiently or permanently become auxotrophic for non-essential or semi-essential amino acids such as asparagine or arginine...
December 5, 2016: Journal of Biotechnology
https://www.readbyqxmd.com/read/27932253/regulation-of-cyclin-d1-by-arsenic-and-microrna-inhibits-adipogenesis
#19
Kevin Beezhold, Linda R Klei, Aaron Barchowsky
Low-dose chronic exposure to arsenic in drinking water represents a global public health concern with established risks for metabolic and cardiovascular disease, as well as cancer. While the linkage between arsenic and disease is strong, further understanding of the molecular mechanisms of its pathogenicity is required. Previous reports demonstrated the ability of arsenic to interfere with adipogenesis, which may mediate its effects in promoting metabolic disease. We hypothesized that microRNA are important regulators of most if not all mesenchymal stem cell processes that are dysregulated by arsenic exposure to impair lipogenesis...
December 5, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27932244/transcriptional-response-to-mitochondrial-protease-immp2l-knockdown-in-human-primary-astrocytes
#20
Akira Gokoolparsadh, Zhiming Fang, Nady Braidy, Peijie Lin, Christopher J Pardy, Valsamma Eapen, Raymond Clarke, Irina Voineagu
IMMP2L encodes the inner membrane peptidase subunit 2, a mitochondrial protease involved in cleaving the space-sorting signals of mitochondrial membrane proteins. IMMP2L has been implicated in Tourette syndrome, but how its dysfunction contributes to the neurodevelopmental phenotype remains unclear. Here we show that IMMP2L transcription requires Topoisomerase I in human primary astrocytes, and characterize the downstream effects of IMMP2L knockdown on gene expression. We demonstrate that IMMP2L knockdown leads to dysregulation of genes involved in central nervous system development...
December 5, 2016: Biochemical and Biophysical Research Communications
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