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Impaired bone marrow microenvironment and stem cells in transfusion-dependent beta-thalassemia.
Zhou, X, Huang, L, Wu, J, Qu, Y, Jiang, H, Zhang, J, Qiu, S, Liao, C, Xu, X, Xia, J, et al
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;:112548
Abstract
Beta-thalassemia (BT) is a hereditary disease caused by abnormal hemoglobin synthesis with consequent ineffective erythropoiesis. Patients with thalassemia major are dependent on long-term blood transfusions with associated long-term complications such as iron overload (IO). This excess iron can result in tissue damage, impaired organ function, and increased morbidity. Growing evidence has demonstrated that IO contributes to impairment of the bone marrow (BM) microenvironment that largely impacts the function of BM mesenchymal stem cells, hematopoietic stem cells, and endothelial cells. In this article, we review recent progress in the understanding of iron metabolism and the perniciousness induced by IO. We highlight the importance of understanding the cross-talk between BM stem cells and the BM microenvironment, particularly the pathological effect of IO on BM stem cells and BT-associated complications. We also provide an update on recent novel therapies to cure transfusion-dependent beta-thalassemia and iron overload-induced complications for their future clinical application.
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p53 tumor suppressor and iron homeostasis.
Zhang, J, Chen, X
The FEBS journal. 2019;(4):620-629
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Abstract
Iron is an essential nutrient for all living organisms and plays a vital role in many fundamental biochemical processes, such as oxygen transport, energy metabolism, and DNA synthesis. Due to its capability to produce free radicals, iron has deleterious effects and thus, its level needs to be tightly controlled in the body. Deregulation of iron metabolism is known to cause diseases, including anemia by iron deficiency and hereditary hemochromatosis by iron overload. Interestingly, dysregulated iron metabolism occurs frequently in tumor cells and contributes to tumorigenesis. In this review, we will discuss the role of p53 tumor suppressor in iron homeostasis.
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Andrographolide Suppresses MV4-11 Cell Proliferation through the Inhibition of FLT3 Signaling, Fatty Acid Synthesis and Cellular Iron Uptake.
Chen, X, Zhang, J, Yuan, L, Lay, Y, Wong, YK, Lim, TK, Ong, CS, Lin, Q, Wang, J, Hua, Z
Molecules (Basel, Switzerland). 2017;(9)
Abstract
Background: Andrographolide (ADR), the main active component of Andrographis paniculata, displays anticancer activity in various cancer cell lines, among which leukemia cell lines exhibit the highest sensitivity to ADR. In particular, ADR was also reported to have reduced drug resistance in multidrug resistant cell lines. However, the mechanism of action (MOA) of ADR's anticancer and anti-drug-resistance activities remain elusive. Methods: In this study, we used the MV4-11 cell line, a FLT3 positive acute myeloid leukemia (AML) cell line that displays multidrug resistance, as our experimental system. We first evaluated the effect of ADR on MV4-11 cell proliferation. Then, a quantitative proteomics approach was applied to identify differentially expressed proteins in ADR-treated MV4-11 cells. Finally, cellular processes and signal pathways affected by ADR in MV4-11 cell were predicted with proteomic analysis and validated with in vitro assays. Results: ADR inhibits MV4-11 cell proliferation in a dose- and time-dependent manner. With a proteomic approach, we discovered that ADR inhibited fatty acid synthesis, cellular iron uptake and FLT3 signaling pathway in MV4-11 cells. Conclusions: ADR inhibits MV4-11 cell proliferation through inhibition of fatty acid synthesis, iron uptake and protein synthesis. Furthermore, ADR reduces drug resistance by blocking FLT3 signaling.
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The Effect of Iron Fortification on Iron (Fe) Status and Inflammation: A Randomized Controlled Trial.
Ma, J, Sun, Q, Liu, J, Hu, Y, Liu, S, Zhang, J, Sheng, X, Hambidge, KM
PloS one. 2016;(12):e0167458
Abstract
BACKGROUND Iron deficiency (ID) is common in toddlers in developing countries. Iron fortified or meat-based complementary foods may be effective to prevent ID. OBJECTIVE Our objective was to compare iron status at 18 months and growth from 6 to 18 months in rural poor toddlers fed 3 different complementary foods. METHODS The study was nested within a larger trial in which 6-month-old infants were randomized to receive 50g/d meat (MG), an equi-caloric fortified cereal supplement (FG) or local cereal supplement (LG) for 1 year. Hb, sTfR, HsCRP, ferritin and AGP were measured in 410 blood samples collected by a random sampling (MG, 137; FG, 140; LG, 133); calprotectin was measured in feces. Body iron = -[log (sTfR ×1000/ferritin)-2.8229] /0.1207. ID = ferritin<12ug/L. RESULTS The toddlers in FG had the significantly highest levels in serum ferritin and body iron (P = 0.043, 0.004), and the rates of both ID and iron deficiency anemia (IDA) were the lowest in FG (P = 0.010, 0.021). The rate of systemic inflammation in FG was 30.71%, which was the highest among three groups (P = 0.042). No intervention effects on either the rates of ID and IDA or iron stores (serum ferritin and body iron) were shown in MG. The change in length-for-age z scores (LAZ) from 6 to 18 months among three groups was significantly different (P = 0.021) and a smaller decrease of LAZ in MG and a larger decrease of LAZ in FG were observed. CONCLUSION Iron fortified cereal improved iron status of poor rural toddlers but was also associated with systemic inflammation which was likely to impair their growth.
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Study on mechanism of algal inactivation and pollution removal by Fe-ACF electro Fenton-like process.
Zhang, J, Wang, H
Water science and technology : a journal of the International Association on Water Pollution Research. 2015;(10):1700-12
Abstract
Algae inactivation and algal metabolic pollutant removal of Chlorella and Duneliella salina from seawater by the Fe-ACF electro Fenton-like process has been studied. The experiments were conducted at neutral condition of pH 8.3 (raw water) and 6.2 to break through the limit of strong acidic conditions. Experimental results indicated that the Fe-ACF electro Fenton-like process has a good effect for algae inactivation and for pollutant removal in neutral conditions, and pH has no obvious effect for the inactivation of algae. At optimum conditions, the inactivation efficiency for algae could reach up to 98%. A pH of 8.3 is more favorable for pollutant removal. Under neutral pH conditions, the coupling effect of indirect oxidation of •OH, direct oxidation of free chlorine and coagulation and adsorption of ferric and ferrous hydroxy complexes in the electro Fenton-like process was achieved, and the coupling effect promotes the inactivation of algae and the removal of metabolic pollutants.
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Enhanced detection and desalting free protocol for phosphopeptides eluted from immobilized Fe (III) affinity chromatography in direct MALDI TOF analysis.
Zhu, L, Zhang, J, Guo, Y
Journal of proteomics. 2014;:360-5
Abstract
UNLABELLED IMAC strategy is widely used in phosphopeptide enrichment, but most of the current eluents contain large amount of salt, which must be discarded before MS detection. Here, we present techniques to elute phosphopeptides with low ionization efficiency reagents, which could be left in the eluate for direct MS analysis, thus saving desalting and the following steps. Several reagents were studied, including 5-sulfosalicylic acid dihydrate, acetyl acetone and glyphosate. The results show that glyphosate has very outstanding advantages: only monophosphopeptides can be eluted with glyphosate solution, while all phosphopeptides can be eluted with negatively charged glyphosate ions with pH9. Moreover, the high ionic strength can minimize nonspecific electrostatic interactions in elution step and limit the generation of potential phosphopeptide-metal ion adducts such as sodium or Fe(3+) counterparts. S/N of phosphopeptides could be enhanced 3-5 folds in MALDI MS detection and phosphopeptide recovery is greatly improved while compared with its counterparts eluted by commonly used elution buffers. By applying this reagent into IMAC elution, the whole experimental process could be more convenient, time-saving and cost-saving, which is of great importance to the enrichment and detection of phosphopeptides in phosphoproteomics research. BIOLOGICAL SIGNIFICANCE This potent desalting-free and signal enhanced elution method can improve the sensitivity and detection of phosphopeptides in MALDI TOF MS analysis, both time saving and cost saving. With these advantages, it's highly appropriate for the high throughout analysis of phosphoproteomics.