Antioxidative Molecules in Human Milk and Environmental Contaminants

Breastfeeding provides overall beneficial health to the mother-child dyad and is universally recognized as the preferred feeding mode for infants up to 6-months and beyond. Human milk provides immuno-protection and supplies nutrients and bioactive compounds whose concentrations vary with lactation stage. Environmental and dietary factors potentially lead to excessive chemical exposure in critical windows of development such as neonatal life, including lactation. This review discusses current knowledge on these environmental and dietary contaminants and summarizes the known effects of these chemicals in human milk, taking into account the protective presence of antioxidative molecules. Particular attention is given to short- and long-term effects of these contaminants, considering their role as endocrine disruptors and potential epigenetic modulators. Finally, we identify knowledge gaps and indicate potential future research directions

Genome sequencing in families with congenital limb malformations

The extensive clinical and genetic heterogeneity of congenital limb malformation calls for comprehensive genome-wide analysis of genetic variation. Genome sequencing (GS) has the potential to identify all genetic variants. Here we aim to determine the diagnostic potential of GS as a comprehensive one-test-for-all strategy in a cohort of undiagnosed patients with congenital limb malformations. We collected 69 cases (64 trios, 1 duo, 5 singletons) with congenital limb malformations with no molecular diagnosis after standard clinical genetic testing and performed genome sequencing. We also developed a framework to identify potential noncoding pathogenic variants. We identified likely pathogenic/disease-associated variants in 12 cases (17.4%) including four in known disease genes, and one repeat expansion in HOXD13. In three unrelated cases with ectrodactyly, we identified likely pathogenic variants in UBA2, establishing it as a novel disease gene. In addition, we found two complex structural variants (3%). We also identified likely causative variants in three novel high confidence candidate genes. We were not able to identify any noncoding variants. GS is a powerful strategy to identify all types of genomic variants associated with congenital limb malformation, including repeat expansions and complex structural variants missed by standard diagnostic approaches. In this cohort, no causative noncoding SNVs could be identified. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00439-021-02295-y

Integrin α6Bβ4 inhibits colon cancer cell proliferation and c-Myc activity

<p>Abstract</p> <p>Background</p> <p>Integrins are known to be important contributors to cancer progression. We have previously shown that the integrin β4 subunit is up-regulated in primary colon cancer. Its partner, the integrin α6 subunit, exists as two different mRNA splice variants, α6A and α6B, that differ in their cytoplasmic domains but evidence for distinct biological functions of these α6 splice variants is still lacking.</p> <p>Methods</p> <p>In this work, we first analyzed the expression of integrin α6A and α6B at the protein and transcript levels in normal human colonic cells as well as colorectal adenocarcinoma cells from both primary tumors and established cell lines. Then, using forced expression experiments, we investigated the effect of α6A and α6B on the regulation of cell proliferation in a colon cancer cell line.</p> <p>Results</p> <p>Using variant-specific antibodies, we observed that α6A and α6B are differentially expressed both within the normal adult colonic epithelium and between normal and diseased colonic tissues. Proliferative cells located in the lower half of the glands were found to predominantly express α6A, while the differentiated and quiescent colonocytes in the upper half of the glands and surface epithelium expressed α6B. A relative decrease of α6B expression was also identified in primary colon tumors and adenocarcinoma cell lines suggesting that the α6A/α6B ratios may be linked to the proliferative status of colonic cells. Additional studies in colon cancer cells showed that experimentally restoring the α6A/α6B balance in favor of α6B caused a decrease in cellular S-phase entry and repressed the activity of c-Myc.</p> <p>Conclusion</p> <p>The findings that the α6Bβ4 integrin is expressed in quiescent normal colonic cells and is significantly down-regulated in colon cancer cells relative to its α6Aβ4 counterpart are consistent with the anti-proliferative influence and inhibitory effect on c-Myc activity identified for this α6Bβ4 integrin. Taken together, these findings point out the importance of integrin variant expression in colon cancer cell biology.</p

Differences in Postprandial Lipid Response to Breast- or Formula-feeding in 8-Week-Old Infants

Objective:Lipids play important roles in infant growth and development. In this exploratory observational single-center study, we investigated postmeal responses of infants to dietary lipids and differences between breast-feeding (BF) and formula-feeding (FF). Methods:Two capillary blood samples were collected from each subject, before and randomly assigned at either 30, 60, 90, 120, 180, or 240 minutes after their respective feeding, followed by measurement of lipid-related plasma parameter concentrations using enzyme-linked immunosorbent assay-based or combined enzymatic and colorimetric methods. Results:The intermeal interval before testing was shorter in the BF (182.9122.85minutes, n=33) versus FF group (214.1 +/- 30.76minutes, n=34); BF subjects fed 5 minutes longer (BF 20.27 +/- 7.7 minutes; FF 14.82 +/- 3.57 minutes). Composite postmeal concentration profiles were generated from 59 plasma sample pairs with sufficient volume (BF=30): triglyceride (TG) baselines were not different. A TG difference was indicated for BF over FF subjects at 30 minutes, for FF over BF subjects at 60 minutes when corrected for baseline. TG responses in both groups appeared and seemed to clear much faster than those reported for adults. The TG:apolipoprotein B48 (ApoB48) ratio suggests that chylomicrons in BF subjects may carry a higher fat load (P Conclusions:Our results indicate that lipids from either BF or FF may be handled differently in young healthy infants

Health-care professionals' approach in feeding term small-for-gestational age infants and its potential implications to later growth outcomes

Aim: To understand feeding practices, nutrition management and postnatal growth monitoring of term small-for-gestational age (tSGA) infants in Southeast Asia. Methods: Anonymous questionnaires to assess practices on feeding, nutrition management and post-natal growth monitoring of tSGA infants were distributed among health-care professionals (HCPs) participating in regional/local perinatology symposia in Malaysia, Thailand and Singapore. Results: Three hundred seventy-seven respondents from Malaysia (37%), Thailand (27%), Singapore (18%) and other Asian countries (19%) participated in the survey. Respondents were neonatologists (35%), paediatricians (25%) and other HCPs (40%) including nurses and midwives. Exclusive human milk feeding was reported the most preferred feeding option for tSGA infants, followed by fortified human milk feeding (60% and 20%, respectively). This was consistent among the different countries. The perceived nutrient requirements of tSGA infants varied between countries. Most respondents from Malaysia and Singapore reported requirements to be similar to preterm infants, while the majority from Thailand reported that it was less than those of preterm infants. The World Health Organization Growth Chart of 2006 and Fenton Growth Charts of 2013 were the most frequently used charts for growth monitoring in the hospital and after discharge. Conclusions: Nutrition management and perceived nutrient requirements for tSGA infants among practising HCPs in Southeast Asia showed considerable variation. The impetus to form standardised and evidence based feeding regimens is important as adequate nutritional management and growth monitoring particularly in this population of infants will have long term impact on population health

Complex lipid globules in early-life nutrition improve long-term metabolic phenotype in intra-uterine growth-restricted rats

hum-uterine growth restriction (IUGR) is associated with adverse metabolic outcome later in life. Healthy mice challenged with a Western-style diet (WSD) accumulated less body fat when previously fed a diet containing large lipid globules (complex lipid matrix (CLM)). This study was designed to clarify whether an early-life CLM diet mitigates 'programmed' visceral adiposity and associated metabolic sequelae after IUGR. In rats, IUGR was induced either by bilateral uterine vessel ligation (LIG) or sham operation (i.e. intra-uterine stress) of the dam on gestational day 19. Offspring from non-operated (NOP) darns served as controls. Male offspring of all groups were either fed CLM or `normal matrix' control diet (CTRL) from postnatal clays (PND) 15 to 42. Thereafter, animals were challenged with a mild WSD until dissection (PND 98). Fat mass (micro computer-tomograph scan: weight of fat compartments), circulating metabolic markers and expression of 'metabolic' genes (quantitative real-time PCR) were assessed. CLM diet significantly reduced visceral fat mass in LIG at PND 40. At dissection, visceral fat mass, fasted blood glucose, TAG and leptin concentrations were significantly increased in LIG-CTRL v. NOP-CTRL, and significantly decreased in LIG-CLM v. LIG-CTRL. Gene expression levels of leptin (mesenteric fat) and insulin-like growth factor 1 (liver) were significantly reduced in LIG-CLM v. LIG-CTRL. In conclusion, early-life CLM diet mitigated the adverse metabolic phenotype after utero-placental insufficiency. The supramolecular structure of dietary lipids may be a novel aspect of nutrient quality that has to be considered in the context of primary prevention of obesity and metabolic disease in at-risk populations