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Recurrent pregnancy loss (RPL) affects 1-2 % of women. Allo- and autoimmune disorders are a recognized factor for RPL and poor pregnancy outcomes. There is a link between antiphospholipid syndrome (APS), Hashimoto's thyroiditis or coeliac disease, and pregnancy losses. The prevalence of the HLA-DQ2/DQ8 polymorphism and genetic susceptibility to the development of celiac disease may be higher in women who experience RPL. A total of 95 women who had experienced two or more miscarriages were qualified into the study: 49 women with the HLA-DQ2/DQ8 polymorphism as the study group, and 46 as the control group. The prenatal test results of the women were evaluated, which revealed that the foetuses from the study group had higher nuchal translucency measurements than those of controls (1.85 mm vs 1.50 mm; p = 0.0024). A higher level of anticardiolipin antibodies (aCL) in the IgG class (18.38 GP L vs 11.37 GP L; p = 0.0039) and antithyroid peroxidase antibodies (aTPO) (87.67 IU/mL vs 11.87 IU/mL; p = 0.0062) was observed when compared to the control group. The presence of the HLA-DQ2.2 polymorphism was observed when higher nuchal translucency measurements and a higher aTPO concentration occurred. A relationship between the aTPO concentration and a higher birth weight of newborns was also shown. No significant differences between the groups were observed for peripheral blood lymphocyte subsets. A statistically significant relationship between the HLA-DQ2/DQ8 polymorphism and the increased concentrations of indicators of autoimmune disorders was indicated., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Cancer vaccination aims at inducing an adaptive immune response against tumor-derived antigens. In this study, we utilize recombinant human adenovirus serotype 5 (rAd5) and recombinant lymphocytic choriomeningitis virus (rLCMV)-based vectors expressing the melanocyte differentiation antigen gp100. In contrast to single or homologous vaccination, a heterologous prime boost vaccination starting with a rAd5-gp100 prime immunization followed by a rLCMV-gp100 boost injection induces a high magnitude of polyfunctional gp100-specific CD8 + T cells. Our data indicate that an optimal T cell induction is dependent on the order and interval of the vaccinations. A prophylactic prime boost vaccination with rAd5- and rLCMV-gp100 protects mice from a B16.F10 melanoma challenge. In the therapeutic setting, combination of the vaccination with low-dose cyclophosphamide showed a synergistic effect and significantly delayed tumor growth. Our findings suggest that heterologous viral vector prime boost immunizations can mediate tumor control in a mouse melanoma model., (© 2020 The Author(s).)

Pregnancy and tobacco smoking (TS) each can cause increases in reactive oxygen species (ROS) production; this, in turn, can lead to disorders in iron management and disruption of the pro- and anti-oxidant balance. The aim of the study was to analyze the influence of TS and Cd on Fe, Zn, and anti-oxidant levels (i.e. glutathione [GSH], metallothionein [MT]) in the blood of pregnant women. The study reported here evaluated 110 blood samples from pregnant women in their 1st, 2nd and 3rd trimester. Concentrations of ferritin and transferrin were measured in the serum; Zn, Fe and cotinine in the plasma, that of Cd in whole blood, that for glutathione in red blood cell lysates, and levels of metallothionein both in the plasma and in lysates prepared from isolated erythrocytes. The results indicated there was a decrease in Zn and increase in Cd and metallothionein levels in pregnant women smokers as compared to in nonsmoking counterparts. Differences in intracellular MT concentration were noted both in smoking and nonsmoking women during pregnancy while there were no changes in extracellular MT level. A decline in circulating ferritin and a rise in transferrin during pregnancy was observed in all groups. Based on the results, it was concluded that exposure to TS-associated xenobiotics like Cd could result in higher MT levels in erythrocytes and in pregnant smokers, the major anti-oxidant mechanism that is in place is one being mediated by MT and not by reduced GSH.

Malaria remains a major challenge to global health causing extensive morbidity and mortality. Yet, there is no efficient vaccine and the immune response remains incompletely understood. Apical Membrane Antigen 1 (AMA1), a leading vaccine candidate, plays a key role during merozoite invasion into erythrocytes by interacting with Rhoptry Neck Protein 2 (RON2). We generated a human anti-AMA1-antibody (humAbAMA1) by EBV-transformation of sorted B-lymphocytes from a Ghanaian donor and subsequent rescue of antibody variable regions. The antibody was expressed in Nicotiana benthamiana and in HEK239-6E, characterized for binding specificity and epitope, and analyzed for its inhibitory effect on Plasmodium falciparum. The generated humAbAMA1 shows an affinity of 106-135 pM. It inhibits the parasite strain 3D7A growth in vitro with an expression system-independent IC 50 -value of 35 μg/ml (95% confidence interval: 33 μg/ml-37 μg/ml), which is three to eight times lower than the IC 50 -values of inhibitory antibodies 4G2 and 1F9. The epitope was mapped to the close proximity of the RON2-peptide binding groove. Competition for binding between the RON2-peptide and humAbAMA1 was confirmed by surface plasmon resonance spectroscopy measurements. The particularly advantageous inhibitory activity of this fully human antibody might provide a basis for future therapeutic applications.

Objectives: Transferrin is a glycosylated protein responsible for transporting iron, an essential metal responsible for proper fetal development. Tobacco is a heavily used xenobiotic having a negative impact on the human body and pregnancy outcomes. Aims of this study was to examine the influence of tobacco smoking on transferrin sialic acid residues and their connection with fetal biometric parameters in women with iron-deficiency., Methods: The study involved 173 samples from pregnant women, smokers and non-smokers, iron deficient and not. Transferrin sialylation was determined by capillary electrophoresis. The cadmium (Cd) level was measured by atomic absorption and the sialic acid concentration by the resorcinol method., Results: Women with iron deficiencies who smoked gave birth earlier than non-smoking, non-iron-deficient women. The Cd level, but not the cotinine level, was positively correlated with transferrin sialylation in the blood of iron-deficient women who smoked; 3-, 4-, 5- and 6-sialoTf correlated negatively with fetal biometric parameters in the same group., Conclusion: It has been shown the relationship between Cd from tobacco smoking and fetal biometric parameters observed only in the iron deficient group suggests an additive effect of these two factors, and indicate that mothers with anemia may be more susceptible to Cd toxicity and disturbed fetal development., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: Tobacco smoking influence on proteins is leading to despaired foetal nourishment. Transferrin, is an essential metal-binding protein responsible for iron transport and proper foetal development. This study examines influence of tobacco smoking on transferrin sialic acid residues and its connection to foetal nourishment at women with iron deficiency., Methods: The study involved 190 samples from pregnant women in 1st, 2nd and 3rd trimester. Women were divided in terms of tobacco smoking and iron deficiency., Results: During pregnancy, the levels of 2-, 5- and 6-sialo transferrin were increasing while 3- and 4-sialo transferrin were decreasing in all groups. Transferrin isoforms showed positive correlation with lowered iron stores in the blood of non-smoking women., Conclusion: Tobacco smoking has an influence on number of sialic acids residues in the transferrin and seems to change conversion of Tf isoforms, and this may disturb iron transport and in consequence influence on foetal development and nourishment., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Tobacco smoking by pregnant women has a negative effect on fetal development and increases pregnancy risk by changing the oxidative balance and microelements level. Smoking affects the concentration, structure and function of proteins, potentially leading to various negative effects on pregnancy outcomes., Methodology/principal Findings: The influence of tobacco smoke on key protein fractions in smoking and non-smoking healthy pregnant women was determined by capillary electrophoresis (CE). Concentrations of the proteins α1-antitrypsin, α1-acid glycoprotein, α2-macroglobulin and transferrin were determined by ELISA tests. Total protein concentration was measured by the Biuret method. Smoking status was established by cotinine levels. Cadmium (Cd) and Zinc (Zn) concentrations were determined by flame atomic absorption spectrometry and the Zn/Cd ratio was calculated based on these numbers. Smoking women had a 3.7 times higher level of Cd than non-smoking women. Zn levels decreased during pregnancy for all women. The Zn/Cd ratio was three times lower in smoking women. The differences between the changes in the protein profile for smoking and non-smoking women were noted. Regarding proteins, α1-antitrypsin and α2-macroglobulin levels were lower in the non-smoking group than in the smoking group and correlated with Cd levels (r = -0.968, p = 0.032 for non-smokers; r = -0.835, p = 0.019 for smokers). Zn/Cd ratios correlated negatively with α1-, α2- and β-globulins., Conclusions/significance: Exposure to tobacco smoke increases the concentration of Cd in the blood of pregnant women and may lead to an elevated risk of pregnancy disorders. During pregnancy alter concentrations of some proteins. The correlation of Cd with proteins suggests that it is one of the causes of protein aberrations., Competing Interests: The authors have declared that no competing interests exist.

Estrogens are female sex hormones, belonging to a group of steroid hormones, derivatives of cholesterol. These hormones can be divided in terms of origin: natural and synthetic. Biologically, the most active is estradiol (E2). Estrogens are responsible for the development of tertiary sexual characteristics and a number of metabolic processes. In our environment there are many substances, metals and toxins which can mimic the biological functions of estrogens. Due to its characteristics, it can induce cell proliferation and stimulate tumor development. Estrogens are subject to a complex metabolism that, inadequately controlled, can lead to toxic derivatives. Catecholestrogens quinones (CE-Q) interact with DNA and form depurinating adducts disturbing cellular processes. By affecting cell proliferation, it can stimulate the formation of mutation and carcinogenesis, by stimulating the production of free radicals exhibiting genotoxicity. Estrogens are mostly used in hormone replacement therapy and hormonal contraception. There are three main sources of administration of preparations containing estrogen: oral, vaginal and percutaneous. The latter two are characterized by a lack of a so-called "first pass effect". Numerous studies carried out on estrogens (both natural and synthetic) demonstrate the possibility of their detrimental function on the human body. Through its impact on clotting factors, it increases the risk of thrombosis and is considered to participate in the formation of cancer of the breast and uterus. That is why the introduction of estrogen therapy should always be preceded by a careful assessment of individual circumstances and the balance between potential benefits and risks.