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- Fritz, Tomas, et al.
(författare)
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Outcome of extremely preterm infants after iatrogenic or spontaneous birth
- 2018
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 97:11, s. 1388-1395
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The risks of preterm birth are known. We investigated the perinatal and infant mortality and morbidity after iatrogenic or spontaneous onset of extremely preterm birth. Material and methods: The present study used data from the population-based EXPRESS study comprising all infants delivered before 27+0 gestational weeks in Sweden between 2004 and 2007. All fetuses alive at admission and with known mode of onset of delivery were included (682 live-born infants; 65 intrapartum deaths). Four multivariate regression models were applied with adjustments for gestational age, fetal gender, multiple pregnancy, and birthweight. Results: After adjustment for gestational age, no significant differences were found between iatrogenic and spontaneous onsets of birth regarding intrapartum death, early neonatal death (0-6 d), or death within 364 days. In the group with iatrogenic onset of delivery, there was an increased risk for severe morbidity (odds ratio [OR] 1.86, 95% confidence interval [95% CI] 1.15-3.02), severe bronchopulmonary dysplasia (OR 1.90, 95% CI 1.10-3.26), and retinopathy of prematurity (OR 1.99, 95% CI 1.21-3.27) after adjustment for gestational age, fetal gender, and multiple pregnancy. After additional adjustment for weight z-scores at 36 gestational weeks, the associations were not significant. Within the group with spontaneous onset of delivery, fetuses with preterm prelabor rupture of membranes had increased mortality risk. Conclusion: No evidence was found for mode of onset of delivery (iatrogenic vs spontaneous) having an impact on neonatal or infant mortality or morbidity in extremely preterm infants. Instead, gestational age and growth deviation at birth seem to be associated with the outcome.
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| 2. |
- Grandoch, Maria, et al.
(författare)
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4-Methylumbelliferone improves the thermogenic capacity of brown adipose tissue
- 2019
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Ingår i: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 1:5, s. 546-559
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic increase in brown adipose tissue (BAT) thermogenesis is of great interest, as BAT activation counteracts obesity and insulin resistance. Hyaluronan (HA) is a glycosaminoglycan, found in the extracellular matrix, that is synthesized by HA synthases (HAS1, HAS2, and HAS3) from sugar precursors and accumulates in diabetic conditions. Its synthesis can be inhibited by the small molecule 4-methylumbelliferone (4-MU). Here we show that inhibition of HA synthesis by 4-MU or genetic deletion of Has2 and Has3 improves the thermogenic capacity of BAT, reduces body-weight gain, and improves glucose homeostasis independently of adrenergic stimulation in mice on a diabetogenic diet. In this context, we validated a novel magnetic resonce T2 mapping approach for in vivo visualization of BAT activation. Inhibition of HA synthesis increases glycolysis, BAT respiration, and uncoupling protein 1 (UCP1) expression. In addition, we show that 4-MU increases BAT capacity without inducing chronic stimulation and propose that 4-MU, a clinically approved, prescription-free drug, could be repurposed to treat obesity and diabetes.
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| 3. |
- Katayama, Mutsumi, et al.
(författare)
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Circulating Exosomal miR-20b-5p is Elevated in Type 2 Diabetes and Could Impair Insulin Action in Human Skeletal Muscle.
- 2019
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 68:3, s. 515-526
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Tidskriftsartikel (refereegranskat)abstract
- MicroRNAs (miRNAs) are noncoding RNAs representing an important class of gene expression modulators. Extracellular circulating miRNAs are both candidate biomarkers for disease pathogenesis and mediators of cell-to-cell communication. We examined the miRNA expression profile of total serum and serum derived exosome-enriched extracellular vesicles in people with normal glucose tolerance or type 2 diabetes. In contrast to total serum miRNA, which did not reveal any differences in miRNA expression, we identified differentially abundant miRNAs in type 2 diabetes patients using miRNA expression profiles of exosome RNA (exoRNA). To validate the role of these differentially abundant miRNAs on glucose metabolism, we transfected miR-20b-5p, a highly abundant exoRNA in type 2 diabetic patients, into primary human skeletal muscle cells. miR-20b-5p overexpression increased basal glycogen synthesis in human skeletal muscle cells. We identified AKTIP and STAT3 as miR-20b-5p targets. miR-20b-5p overexpression reduced AKTIP abundance and insulin-stimulated glycogen accumulation. In conclusion, exosome derived extracellular miR-20b-5p is a circulating biomarker associated with type 2 diabetes, which plays an intracellular role in modulating insulin-stimulated glucose metabolism via AKT signaling.
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