| 1. |
- Andersson, Eva-Lotta, et al.
(author)
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Bile salt-stimulated lipase and pancreatic lipase-related protein 2 : key enzymes for lipid digestion in the newborn examined using the Caco-2 cell line
- 2011
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In: Journal of Lipid Research. - : American Society for Biochemistry and Molecular Biology. - 0022-2275 .- 1539-7262. ; 52:11, s. 1949-1956
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Journal article (peer-reviewed)abstract
- In rodents, bile salt-stimulated lipase (BSSL) and pancreatic lipase-related protein 2 (PLRP2) are the dominant lipases expressed in the exocrine pancreas in early life, when milk is the main food. The aim of the present study was to evaluate if BSSL and PLRP2 are also key enzymes in neonatal intestinal fat digestion. Using Caco-2 cells as a model for the small intestinal epithelium, purified human enzymes were incubated in the apical chamber with substrates and bile salt concentrations resembling the milieu of the small intestine of newborn infants. BSSL and PLRP2 hydrolyzed triglycerides (TG) to free fatty acids (FA) and glycerol. The cells took up the FA, which were reesterfied to TG. Together, BSSL and PLRP2 have a synergistic effect, increasing cellular uptake 4-fold compared to the sum of each lipase alone. A synergistic effect was also observed with retinyl ester as a substrate. PLRP2 hydrolyzed cholesteryl ester but not as efficiently as BSSL, and the two had an additive rather than synergistic effect. We conclude the key enzymes in intestinal fat digestion are different in newborns than later in life. Further studies are needed to fully understand this difference and its implication for designing optimal neonatal nutrition.
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| 2. |
- Andersson, Yvonne, et al.
(author)
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Lactoferrin is responsible for the fungistatic effect of human milk.
- 2000
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In: Early Human Development. - 0378-3782 .- 1872-6232. ; 59:2, s. 95-105
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Journal article (peer-reviewed)abstract
- Human milk has recognized anti-microbial effects and it has been repeatedly shown that breast-fed infants have fewer and less severe infections than formula-fed infants. While most studies have focused on anti-bacterial and anti-viral activities few have focused on the anti-fungal effect of human milk. Dermal and other infections caused by fungi are common in very low birth weight (VLBW) infants. Using a liquid culturing method and Candida albicans and Rhodotorula rubra as representative fungi, we studied the anti-fungal effect of human milk and certain human milk proteins. In vitro, human milk showed potent inhibitory effect on fungal growth. Most, if not all of this effect was caused by lactoferrin via its iron-binding capacity; increasing the iron content of the incubation medium abolished the inhibitory effect. In contrast, other human milk proteins with known or suggested anti-microbial effects rather increased fungal growth. Viability test and electron microscopy revealed that the growth inhibitory effect of human milk, i.e. mediated by lactoferrin, is fungistatic rather than fungicidal.
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| 3. |
- Andersson, Yvonne, et al.
(author)
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Three variants of parathyroid hormone-related protein messenger RNA are expressed in human mammary gland.
- 1997
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In: Pediatric Research. - 0031-3998 .- 1530-0447. ; 41:3, s. 380-3
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Journal article (peer-reviewed)abstract
- PTH-related protein (PTHrP) is found in a variety of tissues; particularly high levels are present in human milk. The structure of the human PTHrP gene is complex, and alternative splicing allows expression of three different variants PTHrP139, PTHrP173, and PTHrP141, respectively. To determine which of the variants are expressed in human mammary gland a reverse transcriptase polymerase chain reaction (RT-PCR) method was elaborated, distinguishing the three variants. mRNA isolated from human milk cells, human mammary epithelial cells (HMEC) and human nonlactating mammary gland cells were analyzed. The RT-PCR experiments resulted in amplification of DNA fragments corresponding to all three variants for all three cell sources tested. The nucleotide sequences of the PCR fragments were determined and verified to be identical to the reported sequences. Hence, it is concluded that human mammary gland epithelial cells express three variants of PTHrP. Whether these have different physiologic effects in the mammary gland or in the breast fed infant remain to be explored.
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| 4. |
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| 5. |
- Esberg, Anders, et al.
(author)
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LIGHT protein : a novel gingival crevicular fluid biomarker associated with increased probing depth after periodontal surgery
- 2024
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In: Journal of Clinical Periodontology. - : John Wiley & Sons. - 0303-6979 .- 1600-051X. ; 51:7, s. 852-862
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Journal article (peer-reviewed)abstract
- Aim: To evaluate the protein profiles in gingival crevicular fluid (GCF) in relation to clinical outcomes after periodontal surgery and examine if any selected proteins affect the mRNA expression of pro-inflammatory cytokines in human gingival fibroblasts.Materials and Methods: This exploratory study included 21 consecutive patients with periodontitis. GCF was collected, and the protein pattern (n = 92) and clinical parameters were evaluated prior to surgery and 3, 6 and 12 months after surgery. Fibroblastic gene expression was analysed by real-time quantitative polymerase chain reaction.Results: Surgical treatment reduced periodontal pocket depth (PPD) and changed the GCF protein pattern. Twelve months after surgery, 17% of the pockets showed an increase in PPD. Levels of a number of proteins in the GCF decreased after surgical treatment but increased with early signs of tissue destruction, with LIGHT being one of the proteins that showed the strongest association. Furthermore, LIGHT up-regulated the mRNA expression of pro-inflammatory cytokines interleukin (IL)-6, IL-8 and MMP9 in human gingival fibroblasts.Conclusions: LIGHT can potentially detect subjects at high risk of periodontitis recurrence after surgical treatment. Moreover, LIGHT induces the expression of inflammatory cytokines and tissue-degrading enzymes in gingival fibroblasts.
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| 6. |
- Esberg, Anders, et al.
(author)
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Serum proteins associated with periodontitis relapse post-surgery: A pilot study
- 2021
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In: Journal of Periodontology. - : John Wiley & Sons. - 0022-3492 .- 1943-3670. ; 92:12, s. 1805-1814
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Journal article (peer-reviewed)abstract
- Background: The knowledge of which genes and proteins that are connected to the susceptibility to gingivitis with subsequent local tissue degradation seen in periodontitis is insufficient. Changes of serum proteins associated with recurrence of bleeding on probing (BOP) and increased periodontal pocket depths (PPD) after surgical treatment of periodontitis could reveal molecules that could be early signals of tissue destruction and/or of importance for systemic effects in other tissues or organs.Methods: We performed a longitudinal pilot study and followed 96 inflammation-related proteins over time in serum from patients who underwent surgical treatment of periodontitis (n= 21). The samples were taken before (time 0), and then at 3, 6, and 12 months after surgery. Changes in protein levels were analysed in relation to the clinical outcome measures, that is, proportion of surfaces affected by BOP and PPD. Results: Changes in treatment outcomes with early signs of relapse in periodontitis after surgical treatment, for example, increased BOP and PPDs, were during 12-months follow up associated with increased serum levels of high-sensitivity C-reactive protein (hs-CRP) and programmed death-ligand 1 (PD-L1), and reduced serum levels of cystatin-D protein.Conclusion: This study shows that clinical signs of recurrence of periodontitis after surgery are reflected in serum, but larger studies are needed for verification. Our novel findings of an association between increased PD-L1- and decreased cystatin D-levels and recurrence in periodontitis are interesting because PD-L1 has been shown to facilitate bacterial infections and chronic inflammation and cystatin D to inhibit tissue destruction. Our results justify mechanistic studies regarding the role of these molecules in periodontitis.
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| 7. |
- Hastie, Roxanne, et al.
(author)
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Low-Dose Aspirin for Preventing Birth of a Small-For-Gestational Age Neonate in a Subsequent Pregnancy.
- 2022
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In: Obstetrics and gynecology. - : Ovid Technologies (Wolters Kluwer Health). - 1873-233X .- 0029-7844. ; 139:4, s. 529-535
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Journal article (peer-reviewed)abstract
- To estimate whether low-dose aspirin use is associated with an altered risk of delivering a small-for-gestational age (SGA) neonate among women with a history of having an SGA neonate in a prior pregnancy.We performed a Swedish register-based cohort study including women in their second pregnancy who had a history of having an SGA neonate (birth weight less than the 10th percentile). The association between use of low-dose aspirin in subsequent pregnancy and birth of an SGA neonate or a severely SGA neonate (birth weight less than the third percentile) were estimated using inverse propensity-weighted estimation, accounting for potential confounders.Among 8,416 women who gave birth to an SGA neonate in their first pregnancy, 801 (9.5%) used low-dose aspirin during their second pregnancy. The incidence of SGA neonates was similar among women using low-dose aspirin (21.7%) and those who did not use aspirin (20.7%). Low-dose aspirin use in pregnancy was not associated with an altered risk of having an SGA neonate (adjusted relative risk [aRR] 0.86, 95% CI 0.67-1.10) or a severely SGA neonate (aRR 0.98, 95% CI 0.71-1.34). Given the strong association between preeclampsia and SGA, we performed subgroup analyses based on preeclampsia status. Among women who had an SGA neonate and co-existing preeclampsia in their first pregnancy, low-dose aspirin was not associated with an altered risk of having an SGA (aRR 0.83, 95% CI 0.63-1.10) or severely SGA (aRR 1.02, 95% CI 0.73-1.44) neonate. Additionally, no association was seen among women who developed preeclampsia in their second pregnancy.Among women with a history of having an SGA neonate, low-dose aspirin was not associated with a decreased risk of having an SGA or severely SGA neonate in subsequent pregnancy. These findings suggest that low-dose aspirin should not be used to prevent recurrent SGA.
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| 8. |
- Johansson, Bente B, et al.
(author)
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Diabetes and pancreatic exocrine dysfunction due to mutations in the carboxyl-ester lipase gene (CEL-MODY) : a protein misfolding disease
- 2011
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In: Journal of Biological Chemistry. - Bethesda, Md. : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 286:40, s. 34593-34605
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Journal article (peer-reviewed)abstract
- CEL-MODY, diabetes with pancreatic lipomatosis and exocrine dysfunction, is due to dominant frame-shift mutations in the acinar cell carboxyl-ester lipase gene (CEL). As Cel knock-out mice do not express the phenotype and the mutant protein has an altered, intrinsically disordered tandem repeat domain, we hypothesized that the disease mechanism might involve a negative effect of the mutant protein. In silico analysis showed that the pI of the tandem repeat was markedly increased from pH 3.3 in wild-type (WT) to 11.8 in mutant (MUT) human CEL. By stably over-expressing CEL-WT and CEL-MUT in HEK293 cells, we found similar glycosylation, ubiquitination, constitutive secretion and quality control of the two proteins. The CEL-MUT protein demonstrated, however, a high propensity to form aggregates found intracellularly and extracellularly. Different physico-chemical properties of the intrinsically disordered tandem repeat domains of WT and MUT proteins may contribute to different short-range and long-range interactions with the globular core domain and other macromolecules, including cell membranes. Thus, we propose that CEL-MODY is a protein misfolding disease caused by a negative gain-of-function effect of the mutant proteins in pancreatic tissues.
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| 9. |
- Li, Xiaonan, et al.
(author)
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Adiponectin and peroxisome proliferator-activated receptor gamma expression in subcutaneous and omental adipose tissue in children
- 2008
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In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 97:5, s. 630-5
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Journal article (peer-reviewed)abstract
- AIM: To compare the expression levels of the adiponectin and peroxisome proliferator -activated receptor gamma (PPARgamma) genes in subcutaneous adipose tissue (SC) and omental adipose tissue (OM) in children with relation to age and anthropometric variables. METHODS: Paired biopsies (SC and OM) were obtained from 53 children (age 0.2-14 years, BMI 12.5-25.8 kg/m(2)). Adiponectin and PPARgamma mRNA levels in adipose tissue were measured by real-time PCR. RESULTS: In overweight, but not in normal weight children, the median adiponectin mRNA level was significantly lower in OM [0.51 (0.1-2.17)] compared to SC [1.29 (0.16-5.08)], (p = 0.03). Adiponectin mRNA levels were strongly associated with PPARgamma mRNA levels in both SC (r = 0.73, p < 0.001) and OM (r = 0.78, p < 0.001). CONCLUSIONS: The lower adiponectin expression in OM relative to SC in overweight children indicates that metabolic-endocrine alterations begin already in childhood. The close association between adiponectin and PPARgamma expression supports the hypothesis this transcription factor is involved in adiponectin gene regulation.
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| 10. |
- Li, Xiaonan, et al.
(author)
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Bile Salt-Stimulated Lipase and Pancreatic Lipase-Related Protein 2 Are the Dominating Lipases in Neonatal Fat Digestion in Mice and Rats.
- 2007
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In: Pediatr Res. - 0031-3998.
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Journal article (peer-reviewed)abstract
- During infancy, the basic conditions for digestion of dietary fat differ from later in life. The bile salt-stimulated lipase (BSSL) is an enzyme expressed in the exocrine pancreas and in some species (including human) also in the lactating mammary gland and secreted with the milk. The aim of this study was to compare the ontogeny of four pancreatic lipases [BSSL, pancreatic triglyceride lipase (PL), pancreatic lipase-related protein 2 (PLRP2), and phospholipase A2 (PLA2)] in one species that supplies BSSL with milk (the mouse) and one that does not (the rat). We followed expression of the four pancreatic lipases from postnatal d 1 until after weaning in both species. We found that BSSL and PLRP2, two lipases with broad substrate specificity, dominated. It was not until weaning that significant expression of PL and PLA2 were induced. Thus, BSSL and PLRP2 seem to be responsible for fat digestion as long as milk is the main food. Moreover, the early temporal pattern of BSSL expression differed between species. We speculate that the milk-borne BSSL is able to compensate for a slower ontogeny of pancreatic BSSL expression in the mouse.PMID: 17805199 [PubMed - as supplied by publisher]
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