The effect of iron deficiency and anaemia on women’s health

Benson, Charlotte; Shah, Akshay; Stanworth, Simon; Frise, Charlotte; Spiby, Helen; Murray, Joanne F.; Klein, A. A.

doi:10.1111/anae.15405

Cited by 82 publications

(68 citation statements)

References 78 publications

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“…Although the reason for this gender difference is not clear, it is interesting that cGMP-related gender effects, e.g., estrogen in the gastrointestinal tract, were already observed in other studies [ 33 ]. Furthermore, iron deficiency and anemia in women are global health problems [ 34 ]. Hence, there might be gender-specific differences in the regulation of the gastrointestinal tract and/or iron-uptake/loss.…”

Section: Discussionmentioning

confidence: 99%

Loss of PKGIβ/IRAG1 Signaling Causes Anemia-Associated Splenomegaly

Majer

Prueschenk

Schlossmann

2021

IJMS

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Inositol 1,4,5triphosphate receptorassociated cGMP kinase substrate 1 (IRAG1) is a substrate protein of the NO/cGMP-signaling pathway and forms a ternary complex with the cGMPdependent protein kinase Iβ (PKGIβ) and the inositol triphosphate receptor I (IP3RI). Functional studies about IRAG1 exhibited that IRAG1 is specifically phosphorylated by the PKGIβ, regulating cGMPmediated IP3dependent Ca2+release. IRAG1 is widely distributed in murine tissues, e.g., in large amounts in smooth muscle-containing tissues and platelets, but also in lower amounts, e.g., in the spleen. The NO/cGMP/PKGI signaling pathway is important in several organ systems. A loss of PKGI causes gastrointestinal disorders, anemia and splenomegaly. Due to the similar tissue distribution of the PKGIβ to IRAG1, we investigated the pathophysiological functions of IRAG1 in this context. Global IRAG1KO mice developed gastrointestinal bleeding, anemiaassociated splenomegaly and iron deficiency. Additionally, Irag1deficiency altered the protein levels of some cGMP/PKGI signaling proteins—particularly a strong decrease in the PKGIβ—in the colon, spleen and stomach but did not change mRNAexpression of the corresponding genes. The present work showed that a loss of IRAG1 and the PKGIβ/IRAG1 signaling has a crucial function in the development of gastrointestinal disorders and anemia-associated splenomegaly. Furthermore, global Irag1deficient mice are possible in vivo model to investigate PKGIβ protein functions.

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Section: Discussionmentioning

confidence: 99%

Loss of PKGIβ/IRAG1 Signaling Causes Anemia-Associated Splenomegaly

Majer

Prueschenk

Schlossmann

2021

IJMS

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“…Iron is a crucial element for mammalian cells responsible for several physiological processes, such as DNA and hemoglobin synthesis, cellular respiration, cell growth, and proliferation [102][103][104][105][106][107]. Iron metabolism is finely regulated by different proteins, such as transferrin (TF), transferrin receptor (TFR-1), ferritin, and ferroportin (FPN-1) [102,103,108]. In particular, TF is an iron-binding protein involved in circulating iron transport [109][110][111].…”

Section: Iron Chelation Effects In Osmentioning

confidence: 99%

Osteosarcoma in Children: Not Only Chemotherapy

et al. 2021

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Osteosarcoma (OS) is the most severe bone malignant tumor, responsible for altered osteoid deposition and with a high rate of metastasis. It is characterized by heterogeneity, chemoresistance and its interaction with bone microenvironment. The 5-year survival rate is about 67% for patients with localized OS, while it remains at 20% in case of metastases. The standard therapy for OS patients is represented by neoadjuvant chemotherapy, surgical resection, and adjuvant chemotherapy. The most used chemotherapy regimen for children is the combination of high-dose methotrexate, doxorubicin, and cisplatin. Considered that the necessary administration of high-dose chemotherapy is responsible for a lot of acute and chronic side effects, the identification of novel therapeutic strategies to ameliorate OS outcome and the patients’ life expectancy is necessary. In this review we provide an overview on new possible innovative therapeutic strategies in OS.

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“…Iron is a very important trace element for organic systems, in particular in literature its vital role is well documented especially in mammal cells [1,2]. Iron is physiologically involved in several biological processes such DNA synthesis and repair, cellular metabolism and signaling [3,4], synthesis of hemoglobin, neurotransmission, cell growth and differentiation, immunity and others [5,6]. Considering the importance of iron in cell biology, a deregulation in its metabolism could damage cells, tissues and organ functions.…”

Section: Introductionmentioning

confidence: 99%

“…Considering the importance of iron in cell biology, a deregulation in its metabolism could damage cells, tissues and organ functions. For this reason, sophisticated molecular mechanisms are necessary to coordinate and maintain a proper homeostasis among iron uptake, utilization, recycling, storage and export [5,7]. Iron levels are normally equal to 3-4 gr with a daily loss of 1-2 mg [8] and these standard range is guaranteed by several key proteins: hepcidin, Ferroportin (FPN-1), ferritin and Transferrin (TF) are the principal regulators [9].…”

Section: Introductionmentioning

confidence: 99%

“…transfusion-dependent thalassemia) [27,28]. Similarly, iron deficiency could cause health problems, among them the most common is iron deficiency anemia [5,29,30], but also cognitive complications in children [31][32][33]. Iron deficiency anemia is a group of sideropenic anemias characterized by low level of iron in plasma, low iron store, low transferrin saturation and other marks [32].…”

Section: Introductionmentioning

confidence: 99%

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Iron Metabolism: From Inflammation to Cancer

A¹,

Tortora²,

Argenziano³

et al. 2021

annhematoloncol

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Iron is a trace element essential for several physiological cell functions and any alteration in its metabolism could be associated to the onset of several disorders. Cells normally avoid any dysregulation, activating fine molecular mechanisms to balance iron uptake, utilization, recycling, storage and export. The main “actors” in this event are hepcidin, ferroportin, ferritin and transferrin, both at cell and systemic level. Dysregulation in iron homeostasis is closely related to inflammation onset and perpetuation, osteoporosis and cancer progression. During inflammation, it has been observed a reduction in circulating iron as direct consequence of increase in ferritin levels, aimed to contain inflammatory processes and in many cases to restore the immune response. Iron overload directly promotes bone resorption and inhibits bone formation inducing osteoporosis. Moreover, iron cellular accumulation is responsible for ROS production with consequent DNA damage and neoplastic transformation of cells. In conclusion, even though many molecular mechanisms have to be clarified, targeting iron and also the mediators of its metabolism could be useful to manage a great variety of disorders, such inflammation, immune diseases, osteoporosis and cancer.

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The effect of iron deficiency and anaemia on women’s health

Cited by 82 publications

References 78 publications

Loss of PKGIβ/IRAG1 Signaling Causes Anemia-Associated Splenomegaly

Loss of PKGIβ/IRAG1 Signaling Causes Anemia-Associated Splenomegaly

Osteosarcoma in Children: Not Only Chemotherapy

Iron Metabolism: From Inflammation to Cancer

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