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https://www.readbyqxmd.com/read/29158088/interplay-of-adipocyte-and-hepatocyte-leptin-upregulates-hepcidin
#1
Kiyoko Yamamoto, Takahiro Kuragano, Tomoko Kimura, Masayoshi Nanami, Yukiko Hasuike, Takeshi Nakanishi
Conflicting evidence concerning leptin, an adipocyte-derived hormone, in atherogenesis and non-alcoholic fatty liver disease (NAFLD) has been reported. Iron metabolism and iron-mediated oxidative stress should be taken into consideration for the clarification of the pathogenesis of these diseases. In this study, we demonstrate that leptin receptor activation directly affects iron metabolism by the finding that serum levels of hepcidin, the master regulator of iron in the whole body, were significantly lower in leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice...
November 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29148036/function-and-mechanism-of-the-pyrin-inflammasome
#2
REVIEW
Rosalie Heilig, Petr Broz
Pyrin, encoded by the MEFV gene, is an intracellular pattern recognition receptor that assembles inflammasome complexes in response to pathogen infections. Mutations in the MEFV gene have been linked to autoinflammatory diseases such as Familial Mediterranean Fever (FMF) or pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND). Recent insights have now revealed how pyrin is activated during infection, providing a molecular basis for the understanding of such disease-causing mutations in pyrin...
November 16, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29134618/the-mechanisms-of-systemic-iron-homeostasis-and-etiology-diagnosis-and-treatment-of-hereditary-hemochromatosis
#3
REVIEW
Hiroshi Kawabata
Hereditary hemochromatosis (HH) is a group of genetic iron overload disorders that manifest with various symptoms, including hepatic dysfunction, diabetes, and cardiomyopathy. Classic HH type 1, which is common in Caucasians, is caused by bi-allelic mutations of HFE. Severe types of HH are caused by either bi-allelic mutations of HFE2 that encodes hemojuvelin (type 2A) or HAMP that encodes hepcidin (type 2B). HH type 3, which is of intermediate severity, is caused by bi-allelic mutations of TFR2 that encodes transferrin receptor 2...
November 13, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29110513/ankaferd-influences-mrna-expression-of-iron-regulated-genes-during-iron-deficiency-anemia
#4
Afife Gulec, Sukru Gulec
Ankaferd Blood Stopper (ABS) comprises a mixture of plants and stops bleeding via forming a protein network by erythroid aggregation. Bleeding causes reduction of iron levels in body. It has been indicated that ABS contains significant amount of iron. Thus, we investigated the biological activity of ABS-derived iron on iron-regulated genes during iron-deficiency anemia (IDA). IDA We selected Caco-2 and HepG2 cell lines as in vitro models of human intestine and liver, respectively. Iron deficiency anemia was induced by deferoxamine...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/29101207/the-ferroportin-disease-pathogenesis-diagnosis-and-treatment
#5
Antonello Pietrangelo
The Ferroportin Disease is an autosomal dominant hereditary iron loading disorder associated with heterozygote mutations of the ferroportin-1 (FPN) gene. It represents one of commonest cause of genetic hyperferritinemia, regardless of ethnicity. FPN1 transfers iron from the intestine, macrophages and placenta into the bloodstream. In the ferroportin disease, loss-of-function mutations of FPN1 limit but do not impair iron-export in enterocytes, but severely affects iron-transfer in macrophages. This leads to progressive and preferential iron trapping in tissue macrophages, reduced iron release to serum transferrin (i...
November 3, 2017: Haematologica
https://www.readbyqxmd.com/read/29092861/effect-of-dietary-palmitic-and-stearic-acids-on-sucrose-motivation-and-hypothalamic-and-striatal-cell-signals-in-the-rat
#6
Dianne P Figlewicz, Jennifer Jay, Constance H West, Aryana Zavosh, Christiane S Hampe, Jared R Radtke, Murray A Raskind, Elaine R Peskind
e have reported that motivation for sucrose is increased in rats fed a moderate (31%) mixed-fat diet for 4-6 weeks. In this study, rats were fed diets containing 32% stearic (STEAR) or palmitic (PALM) acid, and behavior, metabolic profile, and cell signals were compared with those of rats fed a matched low fat (11% fat [LF]) diet. Rats fed STEAR or PALM increased sucrose motivation relative to LF rats (one-way ANOVA for lever presses, p=.03). Diet did not change fasting glucose, insulin, total cholesterol, triglycerides, intravenous glucose tolerance test glucose profile, percent body fat, or total kcal, although kcal as fat were increased (ANOVA p<0...
November 1, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29070017/postdiagnostic-physical-activity-sleep-duration-and-tv-watching-and-all-cause-mortality-among-long-term-colorectal-cancer-survivors-a-prospective-cohort-study
#7
Ilka Ratjen, Clemens Schafmayer, Romina di Giuseppe, Sabina Waniek, Sandra Plachta-Danielzik, Manja Koch, Greta Burmeister, Ute Nöthlings, Jochen Hampe, Sabrina Schlesinger, Wolfgang Lieb
BACKGROUND: Lifestyle recommendations for cancer survivors are warranted to improve survival. In this study, we aimed to examine the association of total physical activity, different types of physical activity, hours of sleeping at day and night, and hours spent watching television (TV) with all-cause mortality in long-term colorectal cancer (CRC) survivors. METHODS: We assessed physical activity in 1376 CRC survivors (44% women; median age, 69 years) at median 6 years after CRC diagnosis using a validated questionnaire...
October 25, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29066846/specific-neurophysiological-mechanisms-underlie-cognitive-inflexibility-in-inflammatory-bowel-disease
#8
Vanessa A Petruo, Sebastian Zeißig, Renate Schmelz, Jochen Hampe, Christian Beste
Inflammatory bowel disease (IBD) is highly prevalent. While the pathophysiological mechanisms of IBD are increasingly understood, there is a lack of knowledge concerning cognitive dysfunctions in IBD. This is all the more the case concerning the underlying neurophysiological mechanisms. In the current study we focus on possible dysfunctions of cognitive flexibility (task switching) processes in IBD patients using a system neurophysiological approach combining event-related potential (ERP) recordings with source localization analyses...
October 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29055010/an-excitable-rho-gtpase-signaling-network-generates-dynamic-subcellular-contraction-patterns
#9
Melanie Graessl, Johannes Koch, Abram Calderon, Dominic Kamps, Soumya Banerjee, Tomáš Mazel, Nina Schulze, Jana Kathrin Jungkurth, Rutuja Patwardhan, Djamschid Solouk, Nico Hampe, Bernd Hoffmann, Leif Dehmelt, Perihan Nalbant
Rho GTPase-based signaling networks control cellular dynamics by coordinating protrusions and retractions in space and time. Here, we reveal a signaling network that generates pulses and propagating waves of cell contractions. These dynamic patterns emerge via self-organization from an activator-inhibitor network, in which the small GTPase Rho amplifies its activity by recruiting its activator, the guanine nucleotide exchange factor GEF-H1. Rho also inhibits itself by local recruitment of actomyosin and the associated RhoGAP Myo9b...
October 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29052181/probiotic-strains-and-mechanistic-insights-for-the-treatment-of-type-2-diabetes
#10
REVIEW
Christiane S Hampe, Christian L Roth
INTRODUCTION: The intestinal microbial composition appears to differ between healthy controls and individuals with Type 2 diabetes (T2D). This observation has led to the hypothesis that perturbations of the intestinal microbiota may contribute to the development of T2D. Manipulations of the intestinal microbiota may therefore provide a novel approach in the prevention and treatment of T2D. Indeed, fecal transplants have shown promising results in both animal models for obesity and T2D and in human clinical trials...
November 2017: Endocrine
https://www.readbyqxmd.com/read/29020610/neonatal-c57bl-6j-and-parkin-mice-respond-differently-following-developmental-manganese-exposure-result-of-a-high-dose-pilot-study
#11
Melanie L Foster, Thomas B Bartnikas, Hailey C Maresca-Fichter, Courtney Mercadante, Miriam Dash, Chelsea Miller, David C Dorman
It has been suggested that childhood exposure to neurotoxicants may increase the risk of Parkinson's disease (PD) or other neurodegenerative disease in adults. Some recessive forms of PD have been linked to loss-of-function mutations in the Park2 gene that encodes for parkin. The purpose of this pilot study was to evaluate whether responses to neonatal manganese (Mn) exposure differ in mice with a Park2 gene defect (parkin mice) when compared with a wildtype strain (C57BL/6J). Neonatal parkin and C57BL/6J littermates were randomly assigned to 0, 11, or 25mg Mn/kg-day dose groups with oral exposures occurring from postnatal day (PND) 1 through PND 28...
October 8, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28978826/progress-in-iron-metabolism-research
#12
Hiroshi Kawabata
Iron is essential for various cellular processes, but an excess of iron may cause organ damage through the production of reactive oxygen species. Therefore, the amount of iron in the body must be strictly controlled. The central regulator of systemic iron homeostasis is hepcidin, which is primarily produced in the liver. Various molecules, including HFE, transferrin receptor 2 (TFR2), and hemojuvelin (HJV), are involved in sensing systemic iron status. Hepatocytes produce hepcidin in response to excess iron and inflammatory stimuli (e...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28953977/an-acquired-mechanism-of-antifungal-drug-resistance-simultaneously-enables-candida-albicans-to-escape-from-intrinsic-host-defenses
#13
Irene A I Hampe, Justin Friedman, Mira Edgerton, Joachim Morschhäuser
The opportunistic fungal pathogen Candida albicans frequently produces genetically altered variants to adapt to environmental changes and new host niches in the course of its life-long association with the human host. Gain-of-function mutations in zinc cluster transcription factors, which result in the constitutive upregulation of their target genes, are a common cause of acquired resistance to the widely used antifungal drug fluconazole, especially during long-term therapy of oropharyngeal candidiasis. In this study, we investigated if C...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28945274/obesity-related-metabolic-disorders-mitigated-by-peptides-designed-to-modulate-adiponectin-assembly
#14
Lutz Hampe, Cheng Xu, Paul W R Harris, Jie Chen, Liu Ming, Martin Middleditch, Mazdak Radjainia, Yu Wang, Alok K Mitra
BACKGROUND AND PURPOSE: Adiponectin, an adipokine possessing profound insulin-sensitizing and anti-inflammatory properties, is a potent biotherapeutic. The trimeric adiponectin subunit assembles into hexameric and functionally important higher-molecular-weight (HMW) forms, tightly controlled by the endoplasmic reticulum protein 44 (ERp44). Obesity-induced ER stress leads to a reduction of the HMW form in serum, contributing to the development of insulin resistance and type2 diabetes. In this study, a panel of designed peptides, targeting ERp44-adiponectin interactions were tested for their effects on the circulating level of HMW adiponectin...
September 25, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28944066/immune-mediated-cerebellar-ataxias-from-bench-to-bedside
#15
REVIEW
Hiroshi Mitoma, Mario Manto, Christiane S Hampe
The cerebellum is a vulnerable target of autoimmunity in the CNS. The category of immune-mediated cerebellar ataxias (IMCAs) was recently established, and includes in particular paraneoplastic cerebellar degenerations (PCDs), gluten ataxia (GA) and anti-GAD65 antibody (Ab) associated-CA, all characterized by the presence of autoantibodies. The significance of onconeuronal autoantibodies remains uncertain in some cases. The pathogenic role of anti-GAD65Ab has been established both in vitro and in vivo, but a consensus has not been reached yet...
2017: Cerebellum & Ataxias
https://www.readbyqxmd.com/read/28935977/zebrafish-in-vivo-screening-for-compounds-amplifying-hematopoietic-stem-and-progenitor-cells-preclinical-validation-in-human-cd34-stem-and-progenitor-cells
#16
Guruchandar Arulmozhivarman, Martin Kräter, Manja Wobus, Jens Friedrichs, Elham Pishali Bejestani, Katrin Müller, Katrin Lambert, Dimitra Alexopoulou, Andreas Dahl, Martin Stöter, Marc Bickle, Nona Shayegi, Jochen Hampe, Friedrich Stölzel, Michael Brand, Malte von Bonin, Martin Bornhäuser
The identification of small molecules that either increase the number and/or enhance the activity of human hematopoietic stem and progenitor cells (hHSPCs) during ex vivo expansion remains challenging. We used an unbiased in vivo chemical screen in a transgenic (c-myb:EGFP) zebrafish embryo model and identified histone deacetylase inhibitors (HDACIs), particularly valproic acid (VPA), as significant enhancers of the number of phenotypic HSPCs, both in vivo and during ex vivo expansion. The long-term functionality of these expanded hHSPCs was verified in a xenotransplantation model with NSG mice...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28930551/uremic-toxins-are-conditional-danger-or-homeostasis-associated-molecular-patterns
#17
Yu Sun, Candice Johnson, Jun Zhou, Luqiao Wang, Ya-Feng Li, Yifan Lu, Gayani Nanayakkara, Hangfei Fu, Ying Shao, Claudette Sanchez, William Y Yang, Xin Wang, Eric T Choi, Rongshan Li, Hong Wang, Xiao-Feng Yang
We mined novel uremic toxin (UT) metabolomics/gene databases, and analyzed the expression changes of UT receptors and UT synthases in chronic kidney disease (CKD) and cardiovascular disease (CVD). We made the following observations: 1) UTs represent only 1/80(th) of human serum small-molecule metabolome; 2) Some UTs are increased in CKD and CVD; 3) UTs either induce or suppress the expression of inflammatory molecules; 4) The expression of UT genes is significantly modulated in CKD patients, and coronary artery disease (CAD) patients; 5) The expression of UT genes is upregulated by caspase-1 and TNF-alpha pathways but is inhibited in regulatory T cells...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28917245/a-single-nucleotide-polymorphism-in-transferrin-is-associated-with-soluble-transferrin-receptor-in-chinese-adolescents
#18
Wei Piao, Li Wang, Ting Zhang, Zhen Wang, Shaofang Shangguan, Jing Sun, Junsheng Huo
BACKGROUND AND OBJECTIVES: Associations between genetic variants in the hepcidin regulation pathway and iron status have been reported in previous studies. Most of these studies were conducted in populations of European descent and relatively few studies have been conducted in Chinese populations. In this study, we evaluated associations between single-nucleotide polymorphisms (SNPs) in the hepcidin regulation pathway, serum ferritin (SF) and soluble transferrin receptor (sTfR) in Chinese adolescents...
2017: Asia Pacific Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28911864/multiscale-approach-to-the-activation-and-phosphotransfer-mechanism-of-cpxa-histidine-kinase-reveals-a-tight-coupling-between-conformational-and-chemical-steps
#19
Franco Marsico, Osvaldo Burastero, Lucas A Defelipe, Elias Daniel Lopez, Mehrnoosh Arrar, Adrián G Turjanski, Marcelo A Marti
Sensor histidine kinases (SHKs) are an integral component of the molecular machinery that permits bacteria to adapt to widely changing environmental conditions. CpxA, an extensively studied SHK, is a multidomain homodimeric protein with each subunit consisting of a periplasmic sensor domain, a transmembrane domain, a signal-transducing HAMP domain, a dimerization and histidine phospho-acceptor sub-domain (DHp) and a catalytic and ATP-binding subdomain (CA). The key activation event involves the rearrangement of the HAMP-DHp helical core and translation of the CA towards the acceptor histidine, which presumably results in an autokinase-competent complex...
September 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28898874/associations-between-liver-enzyme-levels-and-parameters-of-the-metabolic-syndrome-in-obese-children
#20
Christiane S Hampe, Michele L Shaffer, Christian L Roth
BACKGROUND: Obesity is strongly associated with insulin resistance, hypertension, dyslipidemia, and therefore risk for metabolic syndrome (MetS), which is an increasing problem in youth. The potential role of elevated liver enzyme levels in this context needs to be further investigated. METHODS: This paper provides a post hoc analysis of a cross-sectional study of 77 obese nondiabetic children (51% female; median age 11.7 years; BMI >97th percentile) enrolled at the University of Bonn, Bonn, Germany...
2017: Hormone Research in Pædiatrics
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