MicroRNAs (miRNAs) were hypothesized to be robust and easily measured biomarkers of radiation exposure, which has led to multiple studies in various clinical and experimental scenarios. We sought to identify evolutionary conserved, radiation-induced circulating miRNAs through a multispecies, integrative systematic review and meta-analysis of miRNAs in radiation. The systematic review was registered in the PROSPERO database (ID: 81701). We downloaded a list of studies with the query: (circulating OR plasma OR serum) AND (miRNA or microRNA) AND (radiat* OR radiotherapy OR irradiati*) from MEDLINE (103 studies), EMBASE (364 studies), and Cochrane Database of Systematic Reviews (0 studies). After deleting 116 duplicates, the remaining 351 abstracts were reviewed. Inclusion criteria were experimental study; human, mice, rat or nonhuman primate study; and serum or plasma miRNA expression measured before and after radiation exposure. The screening procedure yielded 62 research studies. After verification, 30 articles contained data on miRNA expression change after irradiation. Thus, we obtained a database of 131 miRNAs from 96 pairwise post-/preirradiation comparisons reporting 2508 fold changes (FCs) of circulating miRNAs. The meta-analysis showed 28 miRNAs with significant radiation-induced change of their expression in the serum. In metaregression analysis, 7 miRNAs-miR-150 (FC = 0.40; 95% confidence interval [CI], 0.35-0.45), miR-29a (FC = 0.87; 95% CI, 0.79-0.96), miR-29b (FC = 0.85; 95% CI, 0.76-0.96), miR-30c (FC = 1.19; 95% CI, 1.09-1.30), miR-200b (FC = 1.34; 95% CI, 1.21-1.48), miR-320a (FC = 1.13; 95% CI, 1.05-1.23), and miR-30a (FC = 1.18; 95% CI, 1.07-1.30)-significantly correlated with either total or fraction dose of radiation. Additionally, miR-150, miR-320a, miR-200b, and miR-30c correlated significantly with time elapsed since irradiation. Circulating miRNAs reflect the impact of ionizing radiation irrespective of the studied species, often in a dose-dependent manner. This makes circulating miRNAs promising biomarkers of radiation exposure.

Ncoa4 mediates autophagic degradation of ferritin, the cytosolic iron storage complex, to maintain intracellular iron homeostasis. Recent evidence also supports a role for Ncoa4 in systemic iron homeostasis and erythropoiesis. However, the specific contribution and temporal importance of Ncoa4-mediated ferritinophagy in regulating systemic iron homeostasis and erythropoiesis is unclear. Here, we show that Ncoa4 has a critical role in basal systemic iron homeostasis and both cell autonomous and non-autonomous roles in murine erythropoiesis. Using an inducible murine model of Ncoa4 knockout, acute systemic disruption of Ncoa4 impaired systemic iron homeostasis leading to tissue ferritin and iron accumulation, a decrease in serum iron, and anemia. Mice acutely depleted of Ncoa4 engaged the Hif2α-erythropoietin system to compensate for anemia. Mice with targeted deletion of Ncoa4 specifically in the erythroid compartment developed a pronounced anemia in the immediate postnatal stage, a mild hypochromic microcytic anemia at adult stages, and were more sensitive to hemolysis with higher requirements for the Hif2α-Epo axis and extra-medullary erythropoiesis during recovery. These studies demonstrate the importance of Ncoa4-mediated ferritinophagy as a regulator of systemic iron homeostasis and define the relative cell autonomous and non-autonomous contributions of Ncoa4 in supporting erythropoiesis in vivo.

The aim of the study was to determine the concentration of hexavalent and trivalent chromium, nickel, manganese, and iron in welding fumes (WFs) and to evaluate the significant association between the concentration of metals in the biological material of welders. The studies were conducted in welders (n = 67) and controls (n = 52). Stainless steel WFs were continuously collected in the workers' breathing zone during a shift. The serum and urine concentrations of Cr and Ni were determined by ICP-MS. The content of Mn in the whole blood was determined using ET-AAS. The content of Cr in the erythrocytes was determined using ICP-MS. The Cr concentration in the welders' urine positively correlated with a work environment concentration of Cr (R = 0.59, p < 0.0001), Cr(VI) (R = 0.58, p < 0.0001), and Cr(III) (R = 0.64, p < 0.0001) in the inhalable fraction. The Ni concentration in the welders' urine positively correlated with the Ni concentration in the inhalable and respirable fraction (R = 0.34, p < 0.005 and R = 0.44, p < 0.002). The correlation between the Mn concentration in the work environment air and the Mn concentration in the welders' whole blood (R = 0.46, p < 0.0001) was observed.

Gestational diabetes mellitus (GDM) is a glucose intolerance that begins or is first recognized during pregnancy. It is currently a growing health problem worldwide affecting from 1% to 14% of all pregnant women depending on racial and ethnic group as well as the diagnostic and screening criteria. Our preliminary study aimed at investigating the erythrocyte membrane fatty acid profiles of pregnant women, in particular with diagnosed with gestational diabetes mellitus (GDM), and with normal glucose tolerant (NGT) pregnant women as a control group. The study group comprised 43 pregnant women, 32 of whom were diagnosed with GDM according to the WHO criteria, and 11 with normal glucose tolerance. The erythrocyte membrane phospholipids were obtained according to the Folch extraction procedure. Fatty acids (FA) were analyzed by gas chromatography (GC) as the corresponding fatty acid methyl esters (FAME). A cluster of 14 fatty acids identified contained >98% of the recognized peaks in the GC analysis. The analysis of fatty acids from erythrocytes revealed important differences between GDM and NGT women in the third trimester, and the results were correlated with biochemical data. Among the 14 measured FA representing the membrane lipidomic profile, the levels of three saturated FA (myristic, palmitic, stearic acids) tended to decrease in GDM patients, with the percentage content of stearic acid significantly changed. The relative content of monounsaturated fatty acids (MUFA) tended to increase, in particular the oleic acid and vaccenic acid contents were significantly increased in erythrocyte membranes of the GDM group in comparison with the NGT group. The GDM group demonstrated higher sapienic acid levels (+29%) but this change was not statistically significant. This study revealed association between an impaired cis-vaccenic acid concentration in erythrocytes membrane and GDM development. No significant changes of polyunsaturated fatty acids (PUFA) were observed in GDM and NGT erythrocytes. We postulate, basing on the differences between the GDM and NGT lipidomic profiles, that stearic and cis-vaccenic acids can be considered as dual biomarkers of specific SFA-MUFA conversion pathway, involving the coupling of delta-9 desaturase and elongase enzymes. Our results indicate that the SFA-MUFA families may be involved in the pathophysiology of metabolic diseases such as GDM, but the further studies are needed to confirm our hypothesis. In conclusion, the erythrocyte membranes of GDM women undergo remodeling resulting in abnormal fatty acid profiles, which are reflection of the long-term status of organism and can have great impact on both the mother and her offspring.

Burn induces a systemic response affecting multiple organs, including the liver. Since the liver plays a critical role in metabolic, inflammatory, and immune events, a patient with impaired liver often exhibits poor outcomes. The mortality rate after burns in the elderly population is higher than in any other age group, and studies show that the liver of aged animals is more susceptible to injury after burns. Understanding the aged-specific liver response to burns is fundamental to improving health care. Furthermore, no liver-specific therapy exists to treat burn-induced liver damage highlighting a critical gap in burn injury therapeutics. In this study, we analyzed transcriptomics and metabolomics data from the liver of young and aged mice to identify mechanistic pathways and in-silico predict therapeutic targets to prevent or reverse burn-induced liver damage. Our study highlights pathway interactions and master regulators that underlie the differential liver response to burn injury in young and aged animals.

The present observation based research was designed to evaluate the influence of occupational human exposure to metallic mercury (Hg°) vapor on the biomarkers of selenium status involved in the antioxidant defense system. For this purpose we determined Hg and selenium (Se) concentrations in body fluids, the markers of antioxidant effect measured as an activity of Se-dependent enzymes (red blood cell and plasma glutathione peroxidase: GPx1-RBC and GPx3-P), concentration of selenoprotein P in the plasma (SeP-P) and total antioxidant activity in the plasma (TAA-P) in 131 male workers from a chloralkali plant exposed to Hg° and 67 non-exposed males (control group). The mRNA expression levels of glutathione peroxidases (GPX1, GPX3), selenoprotein P (SEPP1), thioredoxin reductase 1 (TRXR1), thioredoxin 1 (TRX1), peroxiredoxins (PRDX1, PRDX2) were also examined in the leukocytes of peripheral blood. Hg concentration in the blood (Hg-B) and urine (Hg-U) samples was determined using the thermal decomposition amalgamation/atomic absorption spectrometry (TDA-AAS) method and Se concentrations in plasma (Se-P) and urine (Se-U) using the inductively coupled plasma mass spectrometry (ICP-MS) method. Activities of GPx1-RBC, GPx3-P and TAA-P were determined using the kinetic and spectrophotometric method, respectively. Gene expression analysis was performed using the quantitative Real-Time PCR. The results showed significant higher Hg levels among the Hg°-exposed workers in comparison to control group (12-times higher median for Hg-B and almost 74-times higher median for Hg-U concentration in chloralkali workers). Se-P was also significantly higher (Me (median): 82.85 μg/L (IQR (interquartile range) 72.03-90.28 μg/L) for chloralkali workers vs. Me: 72.74 μg/L (IQR 66.25-80.14 μg/L) for control group; p = 0.0001) but interestingly correlated inversely with Hg-U in chloralkali workers suggesting depletion of the Se protection among the workers with the highest Hg-U concentration. The mRNA level for GPX1, PRXD1 were markedly but significantly higher in the workers compared to the control group. Moreover, concentrations of Hg-B and Hg-U among the workers were significantly positively correlated with the levels of selenoprotein P at both the mRNA and selenoprotein levels. In the multivariate model, after adjusting to cofounders (dental amalgam fillings, age, BMI, job seniority time, smoking), we confirmed that Hg-U concentration was inversely correlated with genes expression of TRXR1. This is the first comprehensive assessment of the impact of occupational exposure of workers to Hg° at both the mRNA and selenoprotein levels, with investigation of fish intake obtained by means of a questionnaire. These findings suggest that exposure to Hg° alters gene expression of the antioxidant enzymes and the level of Se-containing selenoproteins.