The Role of the FGF19 Family in the Pathogenesis of Gestational Diabetes: A Narrative Review.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications. Understanding the pathogenesis and appropriate diagnosis of GDM enables the implementation of early interventions during pregnancy that reduce the risk of maternal and fetal complications. At the same time, it provides opportunities to prevent diabetes, metabolic syndrome, and cardiovascular diseases in women with GDM and their offspring in the future. Fibroblast growth factors (FGFs) represent a heterogeneous family of signaling proteins which play a vital role in cell proliferation and differentiation, repair of damaged tissues, wound healing, angiogenesis, and mitogenesis and also affect the regulation of carbohydrate, lipid, and hormone metabolism. Abnormalities in the signaling function of FGFs may lead to numerous pathological conditions, including metabolic diseases. The FGF19 subfamily, also known as atypical FGFs, which includes FGF19, FGF21, and FGF23, is essential in regulating metabolic homeostasis and acts as a hormone while entering the systemic circulation. Many studies have pointed to the involvement of the FGF19 subfamily in the pathogenesis of metabolic diseases, including GDM, although the results are inconclusive. FGF19 and FGF21 are thought to be associated with insulin resistance, an essential element in the pathogenesis of GDM. FGF21 may influence placental metabolism and thus contribute to fetal growth and metabolism regulation. The observed relationship between FGF21 and increased birth weight could suggest a potential role for FGF21 in predicting future metabolic abnormalities in children born to women with GDM. In this group of patients, different mechanisms may contribute to an increased risk of cardiovascular diseases in women in later life, and FGF23 appears to be their promising early predictor. This study aims to present a comprehensive review of the FGF19 subfamily, emphasizing its role in GDM and predicting its long-term metabolic consequences for mothers and their offspring.

Comparative Evaluation of Adipokine Metrics for the Diagnosis of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is one of the most common medical disorders in pregnancy. Adipokines, predominantly secreted by adipose tissue, are involved in numerous metabolic processes. The exact role of adipokines in the pathogenesis of GDM is still not well known, and numerous adipokines have been analysed throughout pregnancy and proposed as biomarkers of GDM. This study aimed to evaluate serum adiponectin, chemerin, lipocalin and apelin levels in GDM and non-GDM women, to assess them as clinically useful biomarkers of the occurrence of GDM and to demonstrate the correlation between the levels of the above adipokines in the blood serum and the increased risk of the development of GDM. The role of these adipokines in the pathogenesis of GDM was also analysed. The statistically significant differences between the levels of adiponectin (7234.6 vs. 9837.5 ng/mL, p < 0.0001), chemerin (264.0 vs. 206.7 ng/mL, p < 0.0001) and lipocalin (39.5 vs. 19.4 ng/mL, p < 0.0001) were observed between pregnant women with GDM and healthy ones. The diagnostic usefulness of the tested adipokines in detecting GDM was also assessed. The research results confirm the hypothesis on the significance of adiponectin, chemerin, lipocalin and apelin in the pathophysiological mechanisms of GDM. We speculate that these adipokines could potentially be established as novel biomarkers for the prediction and early diagnosis of GDM.

The structure of human SFPQ reveals a coiled-coil mediated polymer essential for functional aggregation in gene regulation.

SFPQ, (a.k.a. PSF), is a human tumor suppressor protein that regulates many important functions in the cell nucleus including coordination of long non-coding RNA molecules into nuclear bodies. Here we describe the first crystal structures of Splicing Factor Proline and Glutamine Rich (SFPQ), revealing structural similarity to the related PSPC1/NONO heterodimer and a strikingly extended structure (over 265 Å long) formed by an unusual anti-parallel coiled-coil that results in an infinite linear polymer of SFPQ dimers within the crystals. Small-angle X-ray scattering and transmission electron microscopy experiments show that polymerization is reversible in solution and can be templated by DNA. We demonstrate that the ability to polymerize is essential for the cellular functions of SFPQ: disruptive mutation of the coiled-coil interaction motif results in SFPQ mislocalization, reduced formation of nuclear bodies, abrogated molecular interactions and deficient transcriptional regulation. The coiled-coil interaction motif thus provides a molecular explanation for the functional aggregation of SFPQ that directs its role in regulating many aspects of cellular nucleic acid metabolism.

The design and structural characterization of a synthetic pentatricopeptide repeat protein.

Proteins of the pentatricopeptide repeat (PPR) superfamily are characterized by tandem arrays of a degenerate 35-amino-acid α-hairpin motif. PPR proteins are typically single-stranded RNA-binding proteins with essential roles in organelle biogenesis, RNA editing and mRNA maturation. A modular, predictable code for sequence-specific binding of RNA by PPR proteins has recently been revealed, which opens the door to the de novo design of bespoke proteins with specific RNA targets, with widespread biotechnological potential. Here, the design and production of a synthetic PPR protein based on a consensus sequence and the determination of its crystal structure to 2.2 Šresolution are described. The crystal structure displays helical disorder, resulting in electron density representing an infinite superhelical PPR protein. A structural comparison with related tetratricopeptide repeat (TPR) proteins, and with native PPR proteins, reveals key roles for conserved residues in directing the structure and function of PPR proteins. The designed proteins have high solubility and thermal stability, and can form long tracts of PPR repeats. Thus, consensus-sequence synthetic PPR proteins could provide a suitable backbone for the design of bespoke RNA-binding proteins with the potential for high specificity.

Structure of the heterodimer of human NONO and paraspeckle protein component 1 and analysis of its role in subnuclear body formation.

Proteins of the Drosophila behavior/human splicing (DBHS) family include mammalian SFPQ (PSF), NONO (p54nrb), PSPC1, and invertebrate NONA and Hrp65. DBHS proteins are predominately nuclear, and are involved in transcriptional and posttranscriptional gene regulatory functions as well as DNA repair. DBHS proteins influence a wide gamut of biological processes, including the regulation of circadian rhythm, carcinogenesis, and progression of cancer. Additionally, mammalian DBHS proteins associate with the architectural long noncoding RNA NEAT1 (Menε/ß) to form paraspeckles, subnuclear bodies that alter gene expression via the nuclear retention of RNA. Here we describe the crystal structure of the heterodimer of the multidomain conserved region of the DBHS proteins, PSPC1 and NONO. These proteins form an extensively intertwined dimer, consistent with the observation that the different DBHS proteins are typically copurified from mammalian cells, and suggesting that they act as obligate heterodimers. The PSPC1/NONO heterodimer has a right-handed antiparallel coiled-coil that positions two of four RNA recognition motif domains in an unprecedented arrangement on either side of a 20-Å channel. This configuration is supported by a protein:protein interaction involving the NONA/paraspeckle domain, which is characteristic of the DBHS family. By examining various mutants and truncations in cell culture, we find that DBHS proteins require an additional antiparallel coiled-coil emanating from either end of the dimer for paraspeckle subnuclear body formation. These results suggest that paraspeckles may potentially form through self-association of DBHS dimers into higher-order structures.

Elucidation of asthma phenotypes in atopic teenagers through parallel immunophenotypic and clinical profiling.

BACKGROUND: Current treatment strategies for asthma in teenagers derive primarily from information on chronic disease in adults. More detailed understanding of risk factors related to teenage asthma might aid in the development of improved preventive and treatment strategies for this age group. OBJECTIVE: We sought to identify biomarkers associated with asthma phenotypes in teenagers, particularly atopic asthma, and to identify markers that aid in discriminating between atopic subjects at high versus low risk of asthma. METHODS: We studied 1380 unselected 14-year-olds and collected data on clinical history, allergic sensitization, and respiratory and immunoinflammatory function. The latter comprised measurements of circulating inflammatory markers and in vitro innate and adaptive immune functions, including house dust mite T-cell responses. We integrated the data into regression models to identify variables most strongly associated with asthma risk and severity among atopic subjects. RESULTS: Eight hundred twenty-seven subjects were atopic, 140 subjects were asthmatic, and 81% of asthmatic subjects were also atopic. We identified asthma risk variables related to atopy intensity, including specific IgE and eosinophil levels, plus an additional series external to the T(H)2 cascade but that modified risk only in atopic subjects, including IFN-gamma, IL-10, and IL-12 responses and neutrophil numbers in blood. Moreover, bronchial hyperresponsiveness was associated strongly with atopic but not nonatopic asthma, and the bronchial hyperresponsiveness risk profile was itself dominated by atopy-associated variables. CONCLUSIONS: Asthma in teenagers is predominantly driven by atopy acting in concert with a second tier of T(H)2-independent immunoinflammatory mechanisms, which contribute to pathogenesis only against the background of pre-existing inhalant allergy.

[Sleep apnea syndrome or atrio-ventricular block and hypertension?]. / Bezdech senny czy blok przedsionkowo-komorowy i nadcisnienie tetnicze?

A case of hypertensive patient with obstructive sleep apnea syndrome is presented. The third degree atrio-ventricular block was detected during diagnostic procedure and treatment of blood pressure in patient with obstructive sleep apnea. A heart pacemaker has been implanted. After this procedure the sleep apnea signs have not been detected.

Aortic dissection during pregnancy - obstetric perspective.

The risk of vascular events during pregnancy is substantially increased. Beyond comparatively frequent vascular diseases, pregnancy may lead also to the development of exceptionally rare vascular events such as the aortic dissection and aortic rupture which are conceivably endangering life conditions. Women with the connective tissue disorders and with a family history of the aorta diseases are especially prone to the aortic complications which may also develop in the absence of these risk factors due to the pregnancy-induced structural changes of the aortic wall. The preconception counselling is vital for patients with aortopathies to assess the risk of the aortic dissection and to establish the most appropriate care plan including the surgical intervention. This review presents the management guidelines in patients with the aortic dissection risk during pregnancy.

[Retrospective evaluation of pregnancy in women suffering from systemic lupus erythematosus (SLE)]. / Retrospektywna ocena przebiegu i wyniku ciaz u kobiet z rozpoznaniem tocznia rumieniowatego ukladowego.

OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease predominantly affecting women of childbearing age, which may negatively influence the pregnancy course and outcomes. The objective of the study was to estimate the risk of fetal loss and prematurity in lupus patients. These data seem to be an important component of family counselling in lupus patients. DESIGN: The pregnancies' course and outcomes in lupus patients and in healthy controls were compared. MATERIAL AND METHODS: 47 lupus patients with pregnancies occurring after the diagnosis of SLE and 108 healthy controls were included in this study. The pregnancies were analysed in terms of delivery term and outcomes (live births/ miscarriage/ neonatal deaths/ congenital defects). The structured review and case histories analysis were used to gather the data. RESULTS: The percentage of spontaneous abortions (24.1%) and preterm deliveries (24.1%) were significantly higher in lupus patients when compared with healthy controls (9.3% and 5.3% respectively). CONCLUSIONS: The caution in pregnancy planning in lupus patients is necessary and the role of physicians' information in patients' awareness of fetal loss and prematurity is vital.

[Pregnancy in women with systemic lupus erythematosus (SLE)]. / Przebieg ciazy u kobiet chorujacych na toczen rumieniowaty ukladowy (TRU).

This paper presents the view of literature on pregnancy in systemic lupus erythematosus. It includes opinions on the risk of lupus exacerbation during the pregnancy. Despite much researches, it was not possible to give a precise answer to the question whether pregnancy induces increased rate of lupus flare. The women suffering from SLE face higher risk of fetal losses, preterm births or intrauterine growth retardations. However, if the pregnancy is properly planned and under interdisciplinary medical care, it is highly possible, besides exceptional cases, to give birth to a healthy child. Most of the authors do not advise against pregnancy with lupus patients.

Prion-like domains in RNA binding proteins are essential for building subnuclear paraspeckles.

Prion-like domains (PLDs) are low complexity sequences found in RNA binding proteins associated with the neurodegenerative disorder amyotrophic lateral sclerosis. Recently, PLDs have been implicated in mediating gene regulation via liquid-phase transitions that drive ribonucleoprotein granule assembly. In this paper, we report many PLDs in proteins associated with paraspeckles, subnuclear bodies that form around long noncoding RNA. We mapped the interactome network of paraspeckle proteins, finding enrichment of PLDs. We show that one protein, RBM14, connects key paraspeckle subcomplexes via interactions mediated by its PLD. We further show that the RBM14 PLD, as well as the PLD of another essential paraspeckle protein, FUS, is required to rescue paraspeckle formation in cells in which their endogenous counterpart has been knocked down. Similar to FUS, the RBM14 PLD also forms hydrogels with amyloid-like properties. These results suggest a role for PLD-mediated liquid-phase transitions in paraspeckle formation, highlighting this nuclear body as an excellent model system for understanding the perturbation of such processes in neurodegeneration.

[The level of anxiety, depression and aggression in nurses and their life and job satisfaction]. / Poziom leku, depresji i agresji u pielegniarek, a ich satysfakcja z zycia i z pracy zawodowej.

BACKGROUND: In professions aimed at helping other people such as nursing, an increased level of anxiety, depression and aggression caused by extremely stressful work environment is always possible. It can be hypothesized that these emotions influence nurses' life and job satisfaction, through its decreasing or increasing. MATERIALS AND METHODS: In all, 102 nurses, employed in hospitals, outpatient clinics, hospices and old people's homes, were administered three questionnaires: 1) the Hospital Anxiety and Depression Scale-Modified; 2) the Life Satisfaction Scale; and 3) the job Satisfaction Scale. The survey was a closing part of the course on psychology carried out under the postgraduate education program. RESULTS: The statistical analysis of the results showed the increased level of anxiety in the youngest group of nurses, whereas the level of depression and aggression ranged from medium to low in the whole sample. The nurses' level of job satisfaction was higher than that of their life satisfaction and the differences were statistically significant in each of the three seniority categories. The evaluation of the relationship between life and job satisfaction and anxiety, depression, aggression and job seniority showed: (a) the effect of anxiety and depression, as self-contained factors, on life satisfaction, regardless of job seniority; (b) the effect of aggression interrelated with job seniority on job satisfaction. CONCLUSIONS: Anxiety is the major factor affecting life satisfaction; job satisfaction is less prone to the influence of negative emotions than life satisfaction. Bearing in mind a tendency shown by nurses to suppress their emotions as well as their stressful work environment, they should receive psychological support in its broadest sense.

Assessment of the potency and potential immunomodulatory effects of the measles mumps rubella and varicella vaccine in infants.

This study compared the potency and immunomodulatory effects of measles mumps rubella (MMR) vaccine given to infants alone or in combination with varicella (MMR and V). In an additional group, MMR vaccination was delayed 42 days to permit analysis of potential effects on underlying maturation of systemic immune functions. Assessment of immunity to the vaccines indicated consistent antibody production coupled with mixed Th1/Th2 memory, and no significant differences between vaccine groups or to the group who had their MMR vaccination delayed. Parallel analyses of cytokine responses to phytohaemagglutinin and tetanus toxoid did not detect any "bystander" effects of the vaccines on systemic immunity.

Prenatal versus postnatal sensitization to environmental allergens in a high-risk birth cohort.

BACKGROUND: The timing of allergen sensitization is controversial, with conflicting evidence suggesting transplacental priming versus exclusively postnatal priming. Resolution of this question is important in relation to rational design of allergy prevention strategies, particularly the issue of allergen avoidance during pregnancy. OBJECTIVE: To elucidate the kinetics of sensitization in high-risk children during their first 2 years of life. METHODS: We prospectively studied house dust mite (HDM)-specific IgE and IgG(4) antibody production and associated T-cell immunity in a cohort of 200 high-risk infants. Parallel antibody studies tracked responses against a broader panel of inhalant and dietary allergens including peanut. RESULTS: HDM-induced T(H)2 responses in PBMC from 6 months onward, particularly IL-4 and IL-5, correlated increasingly strongly with sensitization outcomes at 2 years, and a contrasting negative relationship was observed with IFN-gamma response capacity. HDM-induced T-cell responses in cord blood, although common, were unrelated to subsequent sensitization. Transient HDM-IgE (and IgG(4)) production frequently peaked at 6 or 12 months before returning to baseline, which suggests the onset of protective tolerance. This finding contrasted with progressively increasing HDM-IgE titers in children sensitized by 2 years of age. Comparably contrasting patterns were observed in peanut-specific responses in sensitized versus nonsensitized children. CONCLUSION: Priming of T(H)2 responses associated with persistent HDM-IgE production occurs entirely postnatally, as HDM reactivity in cord blood seems nonspecific and is unrelated to subsequent development of allergen-specific T(H)2 memory or IgE. CLINICAL IMPLICATIONS: These findings question the scientific basis for existing recommendations for allergen avoidance by high-risk women during pregnancy.