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https://www.readbyqxmd.com/read/28732358/lenalidomide-restores-the-osteogenic-differentiation-of-bone-marrow-mesenchymal-stem-cells-from-multiple-myeloma-patients-via-deactivating-notch-signaling-pathway
#1
Juan Guo, Chengming Fei, Youshan Zhao, Sida Zhao, Qingqing Zheng, Jiying Su, Dong Wu, Xiao Li, Chunkang Chang
Multiple myeloma (MM) always presents osteolytic bone lesions, resulting from the abnormal osteoblastic and osteoclastic function in patients. MM patients exhibit the impairment of osteogenic differentiation of BMMSCs (bone marrow mesenchymal stem cells) and osteoblast deficiency. Effects of the drug, lenalidomide on the osteoblastic functions and the involved mechanisms remain unexplored. In the present study, it is observed that the osteogenic differentiation of BMMSCs from MM patients (MM-MSCs) is impaired and activation of Notch signaling pathway in MM-MSCs is abnormal...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732180/the-role-of-noncoding-genetic-variation-in-isolated-orofacial-clefts
#2
F Thieme, K U Ludwig
In the past decade, medical genetic research has generated multiple discoveries, many of which were obtained via genome-wide association studies (GWASs). A major GWAS finding is that the majority of risk variants for complex traits map to noncoding regions. This has resulted in a paradigm shift in terms of the interpretation of human genomic sequence variation, with more attention now being paid to what was previously termed "junk DNA." Translation of genetic findings into biologically meaningful results requires 1) large-scale and cell-specific efforts to annotate non-protein-coding regions and 2) the integration of comprehensive genomic data sets...
July 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28731168/osteoclast-regulation-of-osteoblasts-via-rank%C3%A2-rankl-reverse-signal-transduction-in%C3%A2-vitro
#3
Shiqian Zhang, Xiaoyu Wang, Guojun Li, Yang Chong, Jie Zhang, Xinzhen Guo, Baoxin Li, Zhenggang Bi
The treatment of osteoporosis typically inhibits the activity of osteoclasts, which subsequently results in the suppression of bone formation and maintenance, however the underlying mechanism remains to be elucidated. The receptor activator of nuclear factor κ‑B ligand (RANKL)‑receptor activator of nuclear factor κ‑B (RANK) signaling axis is important in the osteoblast regulation of osteoclasts. RANKL surface‑bound molecules expressed on T cells stimulate a reverse signaling transduction in order to regulate the T cells, therefore the present study hypothesized that RANKL expressed on osteoblasts may transfer reverse signals to regulate osteoblasts...
July 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28730953/an-update-on-predicting-severe-hyperbilirubinemia-and-bilirubin-neurotoxicity-risks-in-neonates
#4
Tom Newman, M Jeffrey Maisels
Extreme hyperbilirubinemia and kernicterus, though rare, continue to occur despite the adoption of universal screening. Unless they are known to have glucose-6-phosphate dehydrogenase deficiency, infants who currently develop kernicterus in high resource countries are often otherwise healthy newborns discharged from the well-baby nursery. In this review, we highlight risk factors that increase the risk of a newborn ≥35 weeks gestational age developing severe hyperbilirubinemia, as well as the risk factors that increase the hyperbilirubinemic infant's risk of kernicterus...
July 20, 2017: Current Pediatric Reviews
https://www.readbyqxmd.com/read/28729914/effects-of-mtor-on-neurological-deficits-after-transient-global-ischemia
#5
Jihong Xing, Jian Lu
Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase and activation of its signal pathway plays an important role in regulating protein growth and synthesis as well as cell proliferation and survival. In the present study, we examined the contribution of mTOR and its downstream products to brain injuries and neurological deficiencies after cardiac arrest (CA) induced-transient global ischemia. CA was induced by asphyxia followed by cardiopulmonary resuscitation (CPR) in rats. Our results showed that expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) pathways were amplified in CA rats compared to their controls...
2017: Translational Neuroscience
https://www.readbyqxmd.com/read/28729745/insufficient-angiogenesis-cause-of-abnormally-thin-endometrium-in-subfertile-patients
#6
Joachim Alfer, Lars Happel, Ralf Dittrich, Matthias W Beckmann, Arndt Hartmann, Andreas Gaumann, Volker U Buck, Irmgard Classen-Linke
INTRODUCTION: This study investigated subfertile patients with abnormally thin endometrium after infertility treatment. As they had adequate serum concentrations of hormones, an endometrial factor for subfertility was suspected. METHODS: To elucidate the cause of subfertility, endometrial biopsies were taken in each patient in the late proliferative and mid-secretory phases of one menstrual cycle. Endometrial biopsies from women with normal menstrual cycles and confirmed fertility who were undergoing hysterectomy for benign uterine disease were used as positive controls...
July 2017: Geburtshilfe und Frauenheilkunde
https://www.readbyqxmd.com/read/28729648/a-haplotype-in-cfh-family-genes-confers-high-risk-of-rare-glomerular-nephropathies
#7
Yin Ding, Weiwei Zhao, Tao Zhang, Hao Qiang, Jianping Lu, Xin Su, Shuzhen Wen, Feng Xu, Mingchao Zhang, Haitao Zhang, Caihong Zeng, Zhihong Liu, Huimei Chen
Despite distinct renal lesions, a series of rare glomerular nephropathies are reportedly mediated by complement overactivation. Genetic variations in complement genes contribute to disease risk, but the relationship of genotype to phenotype has not been straightforward. Here, we screened 11 complement genes from 91 patients with atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G) and membranoproliferative glomerulonephritis type I (MPGN I), and identified the concomitant presence of three missense variations located within the human complement Factor H (CFH) gene cluster...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729482/brca1-and-brca2-tumor-suppressors-protect-against-endogenous-acetaldehyde-toxicity
#8
Eliana Mc Tacconi, Xianning Lai, Cecilia Folio, Manuela Porru, Gijs Zonderland, Sophie Badie, Johanna Michl, Irene Sechi, Mélanie Rogier, Verónica Matía García, Ankita Sati Batra, Oscar M Rueda, Peter Bouwman, Jos Jonkers, Anderson Ryan, Bernardo Reina-San-Martin, Joannie Hui, Nelson Tang, Alejandra Bruna, Annamaria Biroccio, Madalena Tarsounas
Maintenance of genome integrity requires the functional interplay between Fanconi anemia (FA) and homologous recombination (HR) repair pathways. Endogenous acetaldehyde, a product of cellular metabolism, is a potent source of DNA damage, particularly toxic to cells and mice lacking the FA protein FANCD2. Here, we investigate whether HR-compromised cells are sensitive to acetaldehyde, similarly to FANCD2-deficient cells. We demonstrate that inactivation of HR factors BRCA1, BRCA2, or RAD51 hypersensitizes cells to acetaldehyde treatment, in spite of the FA pathway being functional...
July 20, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28729433/selective-factor-viii-activation-by-the-tissue-factor-factor-viia-factor-xa-complex
#9
Yuichi Kamikubo, G Loredana Mendolicchio, Antonella Zampolli, Patrizia Marchese, Andrea S Rothmeier, Jennifer Nagrampa Orje, Andrew J Gale, Sriram Krishnaswamy, András Gruber, Henrik Østergaard, Lars C Petersen, Wolfram Ruf, Zaverio M Ruggeri
Safe and effective antithrombotic therapy requires understanding of mechanisms that contribute to pathological thrombosis but have lesser impact on hemostasis. We found that the extrinsic tissue factor (TF) coagulation initiation complex can selectively activate the anti-hemophilic cofactor, FVIII, triggering the hemostatic intrinsic coagulation pathway independently of thrombin feedback loops. In a mouse model with a relatively mild thrombogenic lesion, TF-dependent FVIII activation sets the threshold for thrombus formation through contact phase-generated FIXa...
July 20, 2017: Blood
https://www.readbyqxmd.com/read/28729363/brg1-brahma-related-gene-1-promotes-endothelial-mrtf-transcription-to-establish-embryonic-capillary-integrity
#10
Matthew T Menendez, E-Ching Ong, Brian T Shepherd, Vijay Muthukumar, Robert Silasi-Mansat, Florea Lupu, Courtney T Griffin
OBJECTIVE: The chromatin remodeling enzyme BRG1 (brahma-related gene 1) transcriptionally regulates target genes important for early blood vessel development and primitive hematopoiesis. However, because Brg1 deletion in vascular progenitor cells results in lethal anemia by embryonic day 10.5 (E10.5), roles for BRG1 in embryonic vascular development after midgestation are unknown. In this study, we sought to determine whether endothelial cell BRG1 regulates genes important for vascular development or maintenance later in embryonic development...
July 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28729291/stimulator-of-ifn-genes-mediated-dna-sensing-pathway-is-suppressed-by-nlrp3-agonists-and-regulated-by-mitofusin-1-and-tbc1d15-mitochondria-dynamics-mediators
#11
Dohyeong Kwon, Eunbyeol Park, Suk-Jo Kang
The stimulator of IFN genes (STING)-mediated DNA-sensing pathway plays an important role in the innate immune response to pathogen infection, autoimmunity, and cancer; however, its regulatory mechanism has not been fully elucidated, and we do not yet know whether the STING pathway is counter-regulated by other innate immune pathways. Here, we show that the NLRP3-activating agonists, ATP and nigericin, prevent STING pathway activation in association with mitochondrial fragmentation; however, the suppression of the STING pathway and mitochondria fission were not dependent on NLRP3 or potassium efflux...
July 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28729247/adaptive-regulation-of-pancreatic-acinar-mitochondrial-thiamin-pyrophosphate-uptake-process-possible-involvement-of-epigenetic-mechanism-s
#12
Subrata Sabui, Veedamali S Subramanian, Rubina Kapadia, Hamid M Said
The essentiality of thiamin stems from its roles as a co-factor (mainly in the form of thiamin pyrophosphate, TPP) in critical metabolic reactions including oxidative energy metabolism and reduction of cellular oxidative stress. Like other mammalian cells, pancreatic acinar cells (PAC) obtain thiamin from their surroundings and convert it to TPP; mitochondria then take up TPP by a carrier-mediated process that involves the mitochondrial TPP (MTPP) transporter (MTPPT; product of SLC25A19 gene). Previous studies have characterized different physiological/biological aspects of the MTPP uptake process, but little is known about its possible adaptive-regulation...
July 20, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28729231/cernunnos-deficiency-associated-with-bcg-adenitis-and-autoimmunity-first-case-from-the-national-iranian-registry-and-review-of-the-literature
#13
Reza Yazdani, Hassan Abolhassani, Javad Tafaroji, Gholamreza Azizi, Raif S Geha, Asghar Aghamohammadi
Non-homologous end-joining (NHEJ) is a pathway that repairs double-strand breaks (DSB) in DNA and plays a vital role in V(D)J recombination of immunoglobulin genes. Cernunnos is a DNA repair factor that is involved in nonhomologous end-joining (NHEJ) process. Impairment in Cernunnos leads to a genetic disease characterized by neural disorders, immunodeficiency and increased radiosensitivity. We herein describe a severe combined immunodeficiency (SCID) patient with T- B+ phenotype who had a mutation in Cernunnos gene and manifested recurrent infections, microcephaly and growth retardation with hypogammaglobulinemia...
July 17, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28728941/comparison-of-calcimimetic-r568-and-calcitriol-in-mineral-homeostasis-in-the-hyp-mouse-a-murine-homolog-of-x-linked-hypophosphatemia
#14
Maren Leifheit-Nestler, Julia Kucka, Emi Yoshizawa, Geert Behets, Patrick D'Haese, Christian Bergen, Martin Meier, Dagmar-Christiane Fischer, Dieter Haffner
X-linked hypophosphatemia (XLH) caused by mutations in the Phex gene is the most common human inherited phosphate wasting disorder characterized by enhanced synthesis of fibroblast growth factor 23 (FGF23) in bone, renal phosphate wasting, 1,25(OH)2D3 (1,25D) deficiency, rickets and osteomalacia. Here we studied the effects of calcimimetic R568 and calcitriol treatment in the Hyp mouse, a murine homolog of XLH. We hypothesized that mineral homeostasis is differentially affected by R568 and 1,25D with respect to the PTH-vitamin D-FGF23-Klotho axis and bone health...
July 17, 2017: Bone
https://www.readbyqxmd.com/read/28728890/clinical-influence-of-preoperative-factor-xiii-activity-in-patients-undergoing-pancreatoduodenectomy
#15
Nobuyuki Watanabe, Yukihiro Yokoyama, Tomoki Ebata, Gen Sugawara, Tsuyoshi Igami, Takashi Mizuno, Junpei Yamaguchi, Masato Nagino
BACKGROUND: The influence of decreased factor XIII (FXIII) activity on perioperative bleeding has been reported in some surgical procedures. The purposes of this study were to investigate the perioperative dynamics of FXIII in patients undergoing pancreatoduodenectomy and to clarify the effects of low preoperative FXIII activity on intraoperative bleeding and postoperative complications. METHODS: Total of 43 patients who underwent a pancreatoduodenectomy were enrolled...
July 17, 2017: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/28727954/nutrition-screening-vs-nutrition-assessment-what-s-the-difference
#16
Maria Isabel Toulson Davisson Correia
Screening and assessment imply different processes, with the former indicating risk factors for a deprived nutrition condition and the latter providing the nutrition diagnosis. Both should be routinely performed at hospital admission according to recommended guidelines; however, this is not the reality worldwide, and undernutrition remains highly prevalent in the hospital setting. Therefore, the objective of the current review is to delve into the principles leading to nutrition status deficiencies and how they should be addressed by screening and assessment...
July 1, 2017: Nutrition in Clinical Practice
https://www.readbyqxmd.com/read/28727775/adolescent-health-in-rural-ghana-a-cross-sectional-study-on-the-co-occurrence-of-infectious-diseases-malnutrition-and-cardio-metabolic-risk-factors
#17
Marie Alicke, Justice K Boakye-Appiah, Inusah Abdul-Jalil, Andrea Henze, Markus van der Giet, Matthias B Schulze, Florian J Schweigert, Frank P Mockenhaupt, George Bedu-Addo, Ina Danquah
In sub-Saharan Africa, infectious diseases and malnutrition constitute the main health problems in children, while adolescents and adults are increasingly facing cardio-metabolic conditions. Among adolescents as the largest population group in this region, we investigated the co-occurrence of infectious diseases, malnutrition and cardio-metabolic risk factors (CRFs), and evaluated demographic, socio-economic and medical risk factors for these entities. In a cross-sectional study among 188 adolescents in rural Ghana, malarial infection, common infectious diseases and Body Mass Index were assessed...
2017: PloS One
https://www.readbyqxmd.com/read/28727612/commentary-on-formula-feeding-as-a-risk-factor-for-attention-deficiency-hyperactivity-disorder-is-bisphenol-a-exposure-a-smoking-gun
#18
Michael Weitzman, Lily Lee
No abstract text is available yet for this article.
July 18, 2017: Journal of Developmental and Behavioral Pediatrics: JDBP
https://www.readbyqxmd.com/read/28727110/calibration-and-validation-of-a-carbon-oxidation-system-and-determination-of-the-bicarbonate-retention-factor-and-the-dietary-phenylalanine-requirement-in-the-presence-of-excess-tyrosine-of-adult-female-mixed-breed-dogs
#19
A K Shoveller, J J Danelon, J L Atkinson, G M Davenport, R O Ball, P B Pencharz
Carbon oxidation methods have been used as rapid and sensitive methods to determine whole-body AA requirements in multiple species. The objectives of the current studies were to validate complete CO recovery, determine the bicarbonate retention factor, and estimate the Phe requirement, in the presence of excess Tyr, in adult dogs using the direct oxidation technique. In this series of studies, 2 oxidation chambers were constructed and calibrated to ensure accurate collection of breath CO. First, 104.6 ± 7...
July 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28726785/jun-is-important-for-ocular-hypertension-induced-retinal-ganglion-cell-degeneration
#20
Stephanie B Syc-Mazurek, Kimberly A Fernandes, Richard T Libby
Ocular hypertension, a major risk factor for glaucoma, is thought to trigger glaucomatous neurodegeneration through injury to retinal ganglion cell (RGC) axons. The molecular signaling pathway leading from ocular hypertension to RGC degeneration, however, is not well defined. JNK signaling, a component of the mitogen-activated protein kinase (MAPK) family, and its canonical target, the transcription factor JUN, have been shown to regulate neurodegeneration in many different systems. JUN is expressed after glaucoma-relevant injuries and Jun deficiency protects RGCs after mechanical injury to the optic nerve...
July 20, 2017: Cell Death & Disease
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