Original Research: Use of hydroxyurea and phlebotomy in pediatric patients with hemoglobin SC disease
Hydroxyurea is an excellent therapeutic agent for the pharmacological induction of HbF in patients with sickle cell disease (SCD). However, all completed clinical trials of hydroxyurea have excluded patients with hemoglobin SC (HbSC) disease. HbSC differs significantly in pathophysiology from HbSS, as HbC does not sickle, but instead causes cellular dehydration which potentiates sickling of HbS. Many severely affected HbSC patients have been placed on hydroxyurea on a case by case basis, but there are no large scale prospective data on safety or efficacy of hydroxyurea in this subset of patients with SCD. Here, we report a...
Source: Experimental Biology and Medicine - April 11, 2016 Category: Research Authors: Summarell, C. C. G., Sheehan, V. A. Tags: Articles Source Type: research
Minireview: Prognostic factors and the response to hydroxurea treatment in sickle cell disease
This review describes current considerations in the use of hydroxyurea for the management of sickle cell disease in the context of clinical severity. Randomized trials of hydroxyurea have generally enrolled subjects with increased severity based on frequent vaso-occlusive events. An exception was the BABY HUG study in infants which documented substantial benefit even for asymptomatic subjects. Increasing data indicate that hydroxyurea has a substantial effect on reducing mortality in both adults and children—perhaps the most compelling reason for advocating the drug’s widespread use. Although the efficacy of hy...
Source: Experimental Biology and Medicine - April 11, 2016 Category: Research Authors: Wang, W. C. Tags: Articles Source Type: research
Original Research: Stable expression of miR-34a mediates fetal hemoglobin induction in K562 cells
Sickle cell anemia is a common genetic disorder caused by a point mutation in the sixth codon of the β-globin gene affecting people of African descent worldwide. A wide variety of clinical phenotypes ranging from mild to severe symptoms and complications occur due to hemoglobin S polymerization, red blood cell sickling, and vaso-occlusion. Research efforts are ongoing to develop strategies of fetal hemoglobin (HbF; α22) induction to inhibit sickle hemoglobin polymerization and improve clinical outcomes. Insights have been gained from investigating mutations in the β-globin locus or transcription factors inv...
Source: Experimental Biology and Medicine - April 11, 2016 Category: Research Authors: Ward, C. M., Li, B., Pace, B. S. Tags: Articles Source Type: research
Original Research: A case-control genome-wide association study identifies genetic modifiers of fetal hemoglobin in sickle cell disease
This study identifies possible molecular determinants of HbF production. (Source: Experimental Biology and Medicine)
Source: Experimental Biology and Medicine - April 11, 2016 Category: Research Authors: Liu, L., Pertsemlidis, A., Ding, L.-H., Story, M. D., Steinberg, M. H., Sebastiani, P., Hoppe, C., Ballas, S. K., Pace, B. S. Tags: Articles Source Type: research
Original Research: Generation of non-deletional hereditary persistence of fetal hemoglobin {beta}-globin locus yeast artificial chromosome transgenic mouse models: -175 Black HPFH and -195 Brazilian HPFH
Fetal hemoglobin is a major genetic modifier of the phenotypic heterogeneity in patients with sickle cell disease and certain β-thalassemias. Normal levels of fetal hemoglobin postnatally are approximately 1% of total hemoglobin. Patients who have hereditary persistence of fetal hemoglobin, characterized by elevated synthesis of -globin in adulthood, show reduced disease pathophysiology. Hereditary persistence of fetal hemoglobin is caused by β-globin locus deletions (deletional hereditary persistence of fetal hemoglobin) or -globin gene promoter point mutations (non-deletional hereditary persistence of fetal hem...
Source: Experimental Biology and Medicine - April 11, 2016 Category: Research Authors: Braghini, C. A., Costa, F. C., Fedosyuk, H., Neades, R. Y., Novikova, L. V., Parker, M. P., Winefield, R. D., Peterson, K. R. Tags: Articles Source Type: research
Minireview: Genetic basis of heterogeneity and severity in sickle cell disease
Sickle cell disease, a common single gene disorder, has a complex pathophysiology that at its root is initiated by the polymerization of deoxy sickle hemoglobin. Sickle vasoocclusion and hemolytic anemia drive the development of disease complications. In this review, we focus on the genetic modifiers of disease heterogeneity. The phenotypic heterogeneity of disease is only partially explained by genetic variability of fetal hemoglobin gene expression and co-inheritance of α thalassemia. Given the complexity of pathophysiology, many different definitions of severity are possible complicating a full understanding of it...
Source: Experimental Biology and Medicine - April 11, 2016 Category: Research Authors: Habara, A., Steinberg, M. H. Tags: Articles Source Type: research
Minireview: Clinical severity in sickle cell disease: the challenges of definition and prognostication
Sickle cell disease (SCD) is a monogenic, yet highly phenotypically variable disease with multisystem pathology. This manuscript provides an overview of many of the known determinants, modifiers, and correlates of disease severity in SCD. Despite this wealth of data, modeling the variable and multisystem pathology of SCD continues to be difficult. The current status of prediction of specific adverse outcomes and global disease severity in SCD is also reviewed, highlighting recent successes and ongoing challenges. (Source: Experimental Biology and Medicine)
Source: Experimental Biology and Medicine - April 11, 2016 Category: Research Authors: Quinn, C. T. Tags: Articles Source Type: research
Sickle cell disease severity: an introduction
(Source: Experimental Biology and Medicine)
Source: Experimental Biology and Medicine - April 11, 2016 Category: Research Authors: Pace, B. S., Goodman, S. R. Tags: Introduction Source Type: research
Erratum
Runxia Gu, Chongwen Gong, Honglin Jin, Yao Sun, Zhenyu Li, Jing Chen and Gang Wu. Lysyl oxidase mediates hypoxia-inducedradioresistance in non-small cell lung cancer A549 cells. Experimental Biology and Medicine 2016;241:387–395 (Original doi: 10.1177/1535370215609694) (Source: Experimental Biology and Medicine)
Source: Experimental Biology and Medicine - March 8, 2016 Category: Research Tags: Erratum Source Type: research
Ethanol extract of Zhongtian hawthorn lowers serum cholesterol in mice by inhibiting transcription of 3-hydroxy-3-methylglutaryl-CoA reductase via nuclear factor-kappa B signal pathway
In this study, our results showed that the ethanol extract of Zhongtian hawthorn, a novel grafted cultivar of C. cuneata (wild Shan-Zha), could markedly reduce body weight and levels of serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, and liver cholesterol of hyperlipidemia mice. It could suppress the stimulation effect of high-fat diet on the transcription of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and p65, and counteract the downregulation of CYP7A1 and LDLR. In addition, the results of luciferase reporter assay and Western blot showed that the transcriptional activity of HMGCR promote...
Source: Experimental Biology and Medicine - March 8, 2016 Category: Research Authors: Hu, H.-J., Luo, X.-G., Dong, Q.-Q., Mu, A., Shi, G.-L., Wang, Q.-T., Chen, X.-Y., Zhou, H., Zhang, T.-C., Pan, L.-W. Tags: Pharmacology/Toxicology Source Type: research
Epigallocatechin-3-gallate protects against tumor necrosis factor alpha induced inhibition of osteogenesis of mesenchymal stem cells
Anabolic bone accruement through osteogenic differentiation is important for the maintenance of physiological bone mass and often disrupted in various inflammatory diseases. Epigallocatechin-3-gallate, as an antioxidant and anti-inflammatory agent, has been suggested for potential therapeutic use in this context, possibly by the inhibition of bone resorption as well as the enhancement of bone formation through directly activating osteoblast differentiation. However, the reported effects of epigallocatechin-3-gallate modulating osteoblast differentiation are mixed, and the underlying molecular mechanism is still elusive. Mo...
Source: Experimental Biology and Medicine - March 8, 2016 Category: Research Authors: Liu, W., Fan, J.-B., Xu, D.-W., Zhang, J., Cui, Z.-M. Tags: Pharmacology/Toxicology Source Type: research
Long-term insulin treatment restores cardioprotection induced by sufentanil postconditioning in diabetic rat heart
In conclusion, sufentanil-induced cardioprotection was restored by long-term insulin treatment. The underlying mechanism may be increased phosphorylation of glycogen synthase kinase-3β. (Source: Experimental Biology and Medicine)
Source: Experimental Biology and Medicine - March 8, 2016 Category: Research Authors: Zhang, Y., Zhang, L., Gu, E., Zhu, B., Zhao, X., Chen, J. Tags: Pharmacology/Toxicology Source Type: research
LncRNA TUG1 acts as a tumor suppressor in human glioma by promoting cell apoptosis
This study provided new insights for the function of taurine upregulated gene 1 in cancer biology, and suggested a potent application of taurine upregulated gene 1 overexpression for glioma therapy. (Source: Experimental Biology and Medicine)
Source: Experimental Biology and Medicine - March 8, 2016 Category: Research Authors: Li, J., Zhang, M., An, G., Ma, Q. Tags: Neuroscience Source Type: research
Hydrogen sulfide protects against cognitive impairment induced by hepatic ischemia and reperfusion via attenuating neuroinflammation
In this study, we aim to determine whether sodium hydrosulfide (NaHS), a H2S donor, could alleviate hepatic I/R-induced cognitive impairment and the underlying mechanisms. Rats were injected intraperitoneally with NaHS (5 mg/kg/d) for 11 days. A segmental hepatic I/R model was established on the fourth day. Cognitive function, proinflammatory cytokines levels, and hippocampal ionized calcium-binding adaptor molecule 1 (Iba1) expression was analyzed. We found hepatic I/R increased proinflammatory cytokines levels in serum and hippocampus, up-regulated Iba1 expression, leading to cognitive impairment in rats. However, treatm...
Source: Experimental Biology and Medicine - March 8, 2016 Category: Research Authors: Tu, F., Li, J., Wang, J., Li, Q., Chu, W. Tags: Neuroscience Source Type: research
Anti-inflammatory nutritional intervention in patients with relapsing-remitting and primary-progressive multiple sclerosis: A pilot study
This study indicates that a healthy nutritional intervention is well accepted by people with multiple sclerosis and may ameliorate their physical and inflammatory status. (Source: Experimental Biology and Medicine)
Source: Experimental Biology and Medicine - March 8, 2016 Category: Research Authors: Riccio, P., Rossano, R., Larocca, M., Trotta, V., Mennella, I., Vitaglione, P., Ettorre, M., Graverini, A., De Santis, A., Di Monte, E., Coniglio, M. G. Tags: Endocrinology & amp;amp; Nutrition Source Type: research
