Liver and muscle hemojuvelin are differently glycosylated

<p>Abstract</p> <p>Background</p> <p>Hemojuvelin (HJV) is one of essential components for expression of hepcidin, a hormone which regulates iron transport. HJV is mainly expressed in muscle and liver, and processing of HJV in both tissues is similar. However, hepcidin is expressed in liver but not in muscle and the role of the muscle HJV is yet to be established. Our preliminary analyses of mouse tissue HJV showed that the apparent molecular masses of HJV peptides are different in liver (50 kDa monomer and 35 and 20 kDa heterodimer fragments) and in muscle (55 kDa monomer and a 34 kDa possible large fragment of heterodimer). One possible explanation is glycosylation which could lead to difference in molecular mass.</p> <p>Results</p> <p>We investigated glycosylation of HJV in both liver and muscle tissue from mice. PNGase F treatment revealed that the HJV large fragments of liver and muscle were digested to peptides with similar masses, 30 and 31 kDa, respectively, and the liver 20 kDa small fragment of heterodimer was digested to 16 kDa, while the 50 kDa liver and 55 kDa muscle monomers were reduced to 42 and 48 kDa, respectively. Endo H treatment produced distinct digestion profiles of the large fragment: a small fraction of the 35 kDa peptide was reduced to 33 kDa in liver, while the majority of the 34 kDa peptide was digested to 33 kDa and a very small fraction to 31 kDa in muscle. In addition, liver HJV was found to be neuraminidase-sensitive but its muscle counterpart was neuraminidase-resistant.</p> <p>Conclusions</p> <p>Our results indicate that different oligosaccharides are attached to liver and muscle HJV peptides, which may contribute to different functions of HJV in the two tissues.</p

Distinctive detection of insulinoma using [¹⁸F]FB(ePEG12)12-exendin-4 PET/CT

Specifying the exact localization of insulinoma remains challenging due to the lack of insulinoma-specific imaging methods. Recently, glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging, especially positron emission tomography (PET), has emerged. Although various radiolabeled GLP-1R agonist exendin-4-based probes with chemical modifications for PET imaging have been investigated, an optimal candidate probe and its scanning protocol remain a necessity. Thus, we investigated the utility of a novel exendin-4-based probe conjugated with polyethylene glycol (PEG) for [¹⁸F]FB(ePEG12)12-exendin-4 PET imaging for insulinoma detection. We utilized [¹⁸F]FB(ePEG12)12-exendin-4 PET/CT to visualize mouse tumor models, which were generated using rat insulinoma cell xenografts. The probe demonstrated high uptake value on the tumor as 37.1 ± 0.4%ID/g, with rapid kidney clearance. Additionally, we used Pdx1-Cre;Trp53R172H;Rbf/f mice, which developed endogenous insulinoma and glucagonoma, since they enabled differential imaging evaluation of our probe in functional pancreatic neuroendocrine neoplasms. In this model, our [¹⁸F]FB(ePEG12)12-exendin-4 PET/CT yielded favorable sensitivity and specificity for insulinoma detection. Sensitivity: 30-min post-injection 66.7%, 60-min post-injection 83.3%, combined 100% and specificity: 30-min post-injection 100%, 60-min post-injection 100%, combined 100%, which was corroborated by the results of in vitro time-based analysis of internalized probe accumulation. Accordingly, [¹⁸F]FB(ePEG12)12-exendin-4 is a promising PET imaging probe for visualizing insulinoma

Epidemiologic trends and distributions of imported infectious diseases among travelers to Japan before and during the COVID-19 pandemic, 2016 to 2021: a descriptive study

BACKGROUND: Little is known about the trends of imported infectious diseases among travelers to non-endemic countries during the COVID-19 pandemic. This article aimed to describe those among travelers to Japan. METHODS: This is a descriptive study based on national surveillance data. Imported infectious disease cases were defined as those with a reported overseas source of infection among 15 diseases pre-selected based on the probability and impact of importation. The number of notified cases from April 2016 to March 2021 were described by disease and time of diagnosis. The relative ratio and absolute difference in case counts-both by number and per arrival-were calculated by disease comparing those from the pandemic period (April 2020-March 2021) to the pre-pandemic period (April 2016-March 2020). RESULTS: A total of 3524 imported infectious disease cases were diagnosed during the study period, including 3439 cases before and 85 cases during the pandemic. The proportionate distribution of diseases changed but notification counts of all 15 diseases decreased during the pandemic. Accounting for arrivals, however, seven diseases showed a two-fold or greater increase, with a notable absolute increase per million arrivals for amebiasis (60.1; 95%CI, 41.5-78.7), malaria (21.7; 10.5-33.0), and typhoid fever (9.3; 1.9-16.8). CONCLUSION: The epidemiology of imported infectious diseases changed during the pandemic. While the number of imported infectious disease cases decreased, the number of cases per arrivals increased considerably both in relative and absolute terms for several diseases of public health and clinical importance

Effect of Iron Overload and Iron Deficiency on Liver Hemojuvelin Protein

INTRODUCTION: Hemojuvelin (Hjv) is a key component of the signaling cascade that regulates liver hepcidin (Hamp) expression. The purpose of this study was to determine Hjv protein levels in mice and rats subjected to iron overload and iron deficiency. METHODS: C57BL/6 mice were injected with iron (200 mg/kg); iron deficiency was induced by feeding of an iron-deficient diet, or by repeated phlebotomies. Erythropoietin (EPO)-treated mice were administered recombinant EPO at 50 U/mouse. Wistar rats were injected with iron (1200 mg/kg), or fed an iron-deficient diet. Hjv protein was determined by immunoblotting, liver samples from Hjv-/- mice were used as negative controls. Mouse plasma Hjv content was determined by a commercial ELISA kit. RESULTS: Liver crude membrane fraction from both mice and rats displayed a major Hjv-specific band at 35 kDa, and a weaker band of 20 kDa. In mice, the intensity of these bands was not changed following iron injection, repeated bleeding, low iron diet or EPO administration. No change in liver crude membrane Hjv protein was observed in iron-treated or iron-deficient rats. ELISA assay for mouse plasma Hjv did not show significant difference between Hjv+/+ and Hjv-/- mice. Liver Hamp mRNA, Bmp6 mRNA and Id1 mRNA displayed the expected response to iron overload and iron deficiency. EPO treatment decreased Id1 mRNA, suggesting possible participation of the bone morphogenetic protein pathway in EPO-mediated downregulation of Hamp mRNA. DISCUSSION: Since no differences between Hjv protein levels were found following various experimental manipulations of body iron status, the results indicate that, in vivo, substantial changes in Hamp mRNA can occur without noticeable changes of membrane hemojuvelin content. Therefore, modulation of hemojuvelin protein content apparently does not represent the limiting step in the control of Hamp gene expression