A human anti-matriptase-2 antibody limits iron overload, α-globin aggregates, and splenomegaly in β-thalassemic mice.

Iron plays a major role in the deterioration of β-thalassemia. Indeed, the high levels of transferrin saturation and iron delivered to erythroid progenitors are associated with production of α-globin precipitates that negatively affect erythropoiesis. Matriptase-2/TMPRSS6, a membrane-bound serine protease expressed in hepatocytes, negatively modulates hepcidin production and thus is a key target to prevent iron overload in β-thalassemia.

Associated anomalies in anophthalmia and microphthalmia.

Infants with anophthalmia and microphthalmia (an/microphthalmia) have often other associated congenital anomalies. The reported frequency and the types of these associated anomalies vary between different studies. The purpose of this investigation was to assess the frequency and the types of associated anomalies among cases with an/microphthalmia in a geographically well defined population of northeastern France of 387,067 consecutive pregnancies from 1979 to 2007.

Differences in bone microarchitecture between genetic and secondary iron-overload mouse models suggest a role for hepcidin deficiency in iron-related osteoporosis.

Unlabelled: Iron overload is one of the secondary osteoporosis etiologies. Cellular and molecular mechanisms involved in iron-related osteoporosis are not fully understood.

Aim: The aim of the study was to investigate the respective roles of iron excess and hepcidin, the systemic iron regulator, in the development of iron-related osteoporosis.

Associated anomalies in cases with achondroplasia.

Associated congenital anomalies may be observed in cases with achondroplasia. The prevalence reported in the literature and the types of co-occurring congenital anomalies are variable between the reported studies. The aim of this study was to establish the prevalence and to describe the associated anomalies in cases with achondroplasia.

Co-occurring anomalies in congenital oral clefts.

Oral clefts (OCs) are frequently co-occurring with other non-OC congenital anomalies. The types and the prevalence of anomalies co-occurring with OCs vary in the reported studies. The aims of this report were to study the types and the prevalence of the anomalies co-occurring with OCs in a well-defined population.

Co-occurring non-omphalocele and non-gastroschisis anomalies among cases with congenital omphalocele and gastroschisis.

The pathogenesis of omphalocele and gastroschisis is not obvious. Their etiology is disputed. The prevalence and the types of anomalies co-occurring with omphalocele and gastroschisis are variable in the different series published.

Uropathogenic E. coli induces DNA damage in the bladder.

Urinary tract infections (UTIs) are among the most common outpatient infections, with a lifetime incidence of around 60% in women. We analysed urine samples from 223 patients with community-acquired UTIs and report the presence of the cleavage product released during the synthesis of colibactin, a bacterial genotoxin, in 55 of the samples examined. Uropathogenic Escherichia coli strains isolated from these patients, as well as the archetypal E.

Associated anomalies in cases with congenital clubfoot.

Congenital clubfoot CTEV is a common congenital anomaly, its etiology is unclear and its pathogenesis is controversial. Cases with CTEV often have other non-CTEV associated congenital anomalies. The purpose of this study was to assess the prevalence and the types of these associated anomalies in a defined population.

Associated anomalies in cases with agenesis of the corpus callosum.

Agenesis of corpus callosum (ACC) is an uncommon congenital anomaly, its etiology is unclear and its pathogenesis is controversial. Cases with ACC often have other non-ACC associated congenital anomalies. The purpose of this study was to assess the prevalence and the types of these associated anomalies in a defined population.

Spleen iron, molybdenum, and manganese concentrations are coregulated in hepcidin-deficient and secondary iron overload models in mice.

Iron excess increases the hepatic expression of hepcidin, the systemic iron metabolism regulator that favors iron sequestration in the spleen. Genetic iron overload related to hepcidin insufficiency decreases the spleen iron concentration and increases hepatic iron concentration, whereas during secondary iron overload, the hepcidin expression increases together with spleen iron concentration in addition to hepatic iron concentrations increase. Links between iron metabolism and other metals being suggested, our aim was to investigate, during iron overload, the relationships between the hepatic hepcidin expression level and the hepatic and splenic concentrations of iron, manganese, copper, zinc, and molybdenum, determined using inductively coupled plasma mass spectrometry.

Regulators of hepcidin expression.

Iron, an essential nutrient, is required for many biological processes but is also toxic in excess. The lack of a mechanism to excrete excess iron makes it crucial for the body to regulate the amount of iron absorbed from the diet. This regulation is mediated by the hepatic hormone hepcidin.

Associated anomalies in cases with anorectal anomalies.

Anorectal anomalies (ARA) are common congenital anomalies. The etiology of ARA is unclear and its pathogenesis is controversial. Cases with ARA often have other non-ARA-associated congenital anomalies.

Deletion of BMP6 worsens the phenotype of HJV-deficient mice and attenuates hepcidin levels reached after LPS challenge.

Lack of either bone morphogenetic protein 6 (BMP6) or the BMP coreceptor hemojuvelin (HJV) in mice leads to a similar phenotype with hepcidin insufficiency, hepatic iron loading, and extrahepatic iron accumulation in males. This is consistent with the current views that HJV is a coreceptor for BMP6 in hepatocytes. To determine whether BMP6 and HJV may also signal to hepcidin independently of each other, we intercrossed and mice and compared the phenotype of animals of the F2 progeny.

Associated anomalies in cases with esophageal atresia.

Esophageal atresia (EA) is a common type of congenital anomaly. The etiology of esophageal atresia is unclear and its pathogenesis is controversial. Infants with esophageal atresia often have other non-EA associated congenital anomalies.

Activin inhibition limits early innate immune response in rat kidney allografts-a pilot study.

Activins are members of the transforming growth factor-beta (TGF-β) superfamily of cytokines. They play critical roles in the onset of acute and chronic inflammatory responses. The aim of this study was to investigate how activin inhibition affects acute kidney injury and inflammation after transplantation.

Erythroferrone contributes to hepcidin repression in a mouse model of malarial anemia.

Malaria, a major global health challenge worldwide, is accompanied by a severe anemia secondary to hemolysis and increased erythrophagocytosis. Iron is an essential functional component of erythrocyte hemoglobin and its availability is controlled by the liver-derived hormone hepcidin. We examined the regulation of hepcidin during malarial infection in mice using the rodent parasite Plasmodium berghei K173.

Decreased Bone Formation Explains Osteoporosis in a Genetic Mouse Model of Hemochromatosiss.

Osteoporosis may complicate iron overload diseases such as genetic hemochromatosis. However, molecular mechanisms involved in the iron-related osteoporosis remains poorly understood. Recent in vitro studies support a role of osteoblast impairment in iron-related osteoporosis.

Limiting hepatic Bmp-Smad signaling by matriptase-2 is required for erythropoietin-mediated hepcidin suppression in mice.

Hepcidin, the main regulator of iron homeostasis, is repressed when erythropoiesis is acutely stimulated by erythropoietin (EPO) to favor iron supply to maturing erythroblasts. Erythroferrone (ERFE) has been identified as the erythroid regulator that inhibits hepcidin in stress erythropoiesis. A powerful hepcidin inhibitor is the serine protease matriptase-2, encoded by TMPRSS6, whose mutations cause iron refractory iron deficiency anemia.

Associated congenital anomalies among cases with Down syndrome.

Down syndrome (DS) is the most common congenital anomaly widely studied for at least 150 years. However, the type and the frequency of congenital anomalies associated with DS are still controversial. Despite prenatal diagnosis and elective termination of pregnancy for fetal anomalies, in Europe, from 2008 to 2012 the live birth prevalence of DS per 10,000 was 10.