| 1. |
- Alminger, Marie, 1957, et al.
(författare)
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In Vitro Models for Studying Secondary Plant Metabolite Digestion and Bioaccessibility
- 2014
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Ingår i: Comprehensive Reviews in Food Science and Food Safety. - : Wiley. - 1541-4337. ; 13:4, s. 413-436
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Forskningsöversikt (refereegranskat)abstract
- There is an increased interest in secondary plant metabolites, such as polyphenols and carotenoids, due to their proposed health benefits. Much attention has focused on their bioavailability, a prerequisite for further physiological functions. As human studies are time consuming, costly, and restricted by ethical concerns, in vitro models for investigating the effects of digestion on these compounds have been developed and employed to predict their release from the food matrix, bioaccessibility, and assess changes in their profiles prior to absorption. Most typically, models simulate digestion in the oral cavity, the stomach, the small intestine, and, occasionally, the large intestine. A plethora of models have been reported, the choice mostly driven by the type of phytochemical studied, whether the purpose is screening or studying under close physiological conditions, and the availability of the model systems. Unfortunately, the diversity of model conditions has hampered the ability to compare results across different studies. For example, there is substantial variability in the time of digestion, concentrations of salts, enzymes, and bile acids used, pH, the inclusion of various digestion stages; and whether chosen conditions are static (with fixed concentrations of enzymes, bile salts, digesta, and so on) or dynamic (varying concentrations of these constituents). This review presents an overview of models that have been employed to study the digestion of both lipophilic and hydrophilic phytochemicals, comparing digestive conditions in vitro and in vivo and, finally, suggests a set of parameters for static models that resemble physiological conditions.
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| 4. |
- Nilsson, Gisela M A, 1973, et al.
(författare)
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Two different isoforms of osteopontin modulate myelination and axonal integrity
- 2023
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Ingår i: Faseb Bioadvances. - 2573-9832. ; 5:8, s. 336-353
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Tidskriftsartikel (refereegranskat)abstract
- Abnormal myelination underlies the pathology of white matter diseases such as preterm white matter injury and multiple sclerosis. Osteopontin (OPN) has been suggested to play a role in myelination. Murine OPN mRNA is translated into a secreted isoform (sOPN) or an intracellular isoform (iOPN). Whether there is an isoform-specific involvement of OPN in myelination is unknown. Here we generated mouse models that either lacked both OPN isoforms in all cells (OPN-KO) or lacked sOPN systemically but expressed iOPN specifically in oligodendrocytes (OLs-iOPN-KI). Transcriptome analysis of isolated oligodendrocytes from the neonatal brain showed that genes and pathways related to increase of myelination and altered cell cycle control were enriched in the absence of the two OPN isoforms in OPN-KO mice compared to control mice. Accordingly, adult OPN-KO mice showed an increased axonal myelination, as revealed by transmission electron microscopy imaging, and increased expression of myelin-related proteins. In contrast, neonatal oligodendrocytes from OLs-iOPN-KI mice compared to control mice showed differential regulation of genes and pathways related to the increase of cell adhesion, motility, and vasculature development, and the decrease of axonal/neuronal development. OLs-iOPN-KI mice showed abnormal myelin formation in the early phase of myelination in young mice and signs of axonal degeneration in adulthood. These results suggest an OPN isoform-specific involvement, and a possible interplay between the isoforms, in myelination, and axonal integrity. Thus, the two isoforms of OPN need to be separately considered in therapeutic strategies targeting OPN in white matter injury and diseases.
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| 5. |
- Zelco, Aura, et al.
(författare)
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Single-cell atlas reveals meningeal leukocyte heterogeneity in the developing mouse brain.
- 2021
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Ingår i: Genes & development. - : Cold Spring Harbor Laboratory. - 1549-5477 .- 0890-9369. ; 35:15-16, s. 1190-1207
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Tidskriftsartikel (refereegranskat)abstract
- The meninges are important for brain development and pathology. Using single-cell RNA sequencing, we have generated the first comprehensive transcriptional atlas of neonatal mouse meningeal leukocytes under normal conditions and after perinatal brain injury. We identified almost all known leukocyte subtypes and found differences between neonatal and adult border-associated macrophages, thus highlighting that neonatal border-associated macrophages are functionally immature with regards to immune responses compared with their adult counterparts. We also identified novel meningeal microglia-like cell populations that may participate in white matter development. Early after the hypoxic-ischemic insult, neutrophil numbers increased and they exhibited increased granulopoiesis, suggesting that the meninges are an important site of immune cell expansion with implications for the initiation of inflammatory cascades after neonatal brain injury. Our study provides a single-cell resolution view of the importance of meningeal leukocytes at the early stage of development in health and disease.
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| 6. |
- Gourevitch, Jesse D., et al.
(författare)
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Projected losses of ecosystem services in the US disproportionately affect non-white and lower-income populations
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Addressing how ecosystem services (ES) are distributed among groups of people is critical for making conservation and environmental policy-making more equitable. Here, we evaluate the distribution and equity of changes in ES benefits across demographic and socioeconomic groups in the United States (US) between 2020 and 2100. Specifically, we use land cover and population projections to model potential shifts in the supply, demand, and benefits of the following ES: provision of clean air, protection against a vector-borne disease (West Nile virus), and crop pollination. Across the US, changes in ES benefits are unevenly distributed among socioeconomic and demographic groups and among rural and urban communities, but are relatively uniform across geographic regions. In general, non-white, lower-income, and urban populations disproportionately bear the burden of declines in ES benefits. This is largely driven by the conversion of forests and wetlands to cropland and urban land cover in counties where these populations are expected to grow. In these locations, targeted land use policy interventions are required to avoid exacerbating inequalities already present in the US.
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| 7. |
- Harding-Esch, Emma M., et al.
(författare)
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Impact of a single round of mass drug administration with azithromycin on active trachoma and ocular Chlamydia trachomatis prevalence and circulating strains in The Gambia and Senegal
- 2019
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Ingår i: Parasites & Vectors. - : BMC. - 1756-3305. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mass drug administration (MDA) with azithromycin is a cornerstone of the trachoma elimination strategy. Although the global prevalence of active trachoma has declined considerably, prevalence persists or even increases in some communities and districts. To increase understanding of MDA impact, we investigated the prevalence of active trachoma and ocular C. trachomatis prevalence, organism load, and circulating strains at baseline and one-year post-MDA in The Gambia and Senegal.Methods: Pre- and one-year post-MDA, children aged 0-9 years were examined for clinical signs of trachoma in six Gambian and 12 Senegalese villages. Ocular swabs from each child's right conjunctiva were tested for evidence of ocular C. trachomatis infection and organism load (ompA copy number), and ompA and multi-locus sequence typing (MLST) was performed.Results: A total of 1171 children were examined at baseline and follow-up in The Gambia. Active trachoma prevalence decreased from 23.9% to 17.7%, whereas ocular C. trachomatis prevalence increased from 3.0% to 3.8%. In Senegal, 1613 and 1771 children were examined at baseline and follow-up, respectively. Active trachoma prevalence decreased from 14.9% to 8.0%, whereas ocular C. trachomatis prevalence increased from 1.8% to 3.6%. Higher organism load was associated with having active trachoma and severe inflammation. Sequence typing demonstrated that all Senegalese samples were genovar A, whereas Gambian samples were a mix of genovars A and B. MLST provided evidence of clustering at village and household levels and demonstrated differences of strain variant frequencies in Senegal, indicative of an "outbreak". MLST, including partial ompA typing, provided greater discriminatory power than complete ompA typing.Conclusions: We found that one round of MDA led to an overall decline in active trachoma prevalence but no impact on ocular C. trachomatis infection, with heterogeneity observed between villages studied. This could not be explained by MDA coverage or number of different circulating strains pre- and post-MDA. The poor correlation between active trachoma and infection prevalence supports the need for further work on alternative indicators to clinical signs for diagnosing ocular C. trachomatis infection. MLST typing has potential molecular epidemiology utility, including better understanding of transmission dynamics, although relationship to whole-genome sequence variability requires further exploration.
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| 8. |
- Nazmi, Arshed, et al.
(författare)
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Lymphocytes Contribute to the Pathophysiology of Neonatal Brain Injury
- 2018
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 9, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Periventricular leukomalacia (PVL) is the most common form of preterm brain injury affecting the cerebral white matter. This type of injury involves a multiphase process and is induced by many factors, including hypoxia-ischemia (HI) and infection. Previous studies have suggested that lymphocytes play a significant role in the pathogenesis of brain injury, and the aim of this study was to determine the contribution of lymphocyte subsets to preterm brain injury.Immunohistochemistry on brain sections from neonatal mice was performed to evaluate the extent of brain injury in wild-type and T cell and B cell-deficient neonatal mice (Rag1-/- mice) using a mouse model of HI-induced preterm brain injury. Flow cytometry was performed to determine the presence of different types of immune cells in mouse brains following HI. In addition, immunostaining for CD3 T cells and CD20 B cells was performed on postmortem preterm human infant brains with PVL.Mature lymphocyte-deficient Rag1- / - mice showed protection from white matter loss compared to wild type mice as indicated by myelin basic protein immunostaining of mouse brains. CD3+ T cells and CD20+ B cells were observed in the postmortem preterm infant brains with PVL. Flow cytometry analysis of mouse brains after HI-induced injury showed increased frequency of CD3+ T, αβT and B cells at 7days after HI in the ipsilateral (injured) hemisphere compared to the contralateral (control, uninjured) hemisphere.Lymphocytes were found in the injured brain after injury in both mice and humans, and lack of mature lymphocytes protected neonatal mice from HI-induced brain white matter injury. This finding provides insight into the pathology of perinatal brain injury and suggests new avenues for the development of therapeutic strategies.
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| 9. |
- Song, Juan, et al.
(författare)
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Temporal brain transcriptome analysis reveals key pathological events after germinal matrix hemorrhage in neonatal rats
- 2022
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 42:9, s. 1632-1649
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Tidskriftsartikel (refereegranskat)abstract
- Germinal matrix hemorrhage (GMH) is a common complication in preterm infants and is associated with high risk of adverse neurodevelopmental outcomes. We used a rat GMH model and performed RNA sequencing to investigate the signaling pathways and biological processes following hemorrhage. GMH induced brain injury characterized by early hematoma and subsequent tissue loss. At 6 hours after GMH, gene expression indicated an increase in mitochondrial activity such as ATP metabolism and oxidative phosphorylation along with upregulation of cytoprotective pathways and heme metabolism. At 24 hours after GMH, the expression pattern suggested an increase in cell cycle progression and downregulation of neurodevelopmental-related pathways. At 72 hours after GMH, there was an increase in genes related to inflammation and an upregulation of ferroptosis. Hemoglobin components and genes related to heme metabolism and ferroptosis such as Hmox1, Alox15, and Alas2 were among the most upregulated genes. We observed dysregulation of processes involved in development, mitochondrial function, cholesterol biosynthesis, and inflammation, all of which contribute to neurodevelopmental deterioration following GMH. This study is the first temporal transcriptome profile providing a comprehensive overview of the molecular mechanisms underlying brain injury following GMH, and it provides useful guidance in the search for therapeutic interventions.
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| 10. |
- Zelco, Aura, et al.
(författare)
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Type 2 Innate Lymphoid Cells Accumulate in the Brain After Hypoxia-Ischemia but Do Not Contribute to the Development of Preterm Brain Injury.
- 2020
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Ingår i: Frontiers in cellular neuroscience. - : Frontiers Media SA. - 1662-5102. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- The immune system of human and mouse neonates is relatively immature. However, innate lymphoid cells (ILCs), commonly divided into the subsets ILC1, ILC2, and ILC3, are already present in the placenta and other fetal compartments and exhibit higher activity than what is seen in adulthood. Recent reports have suggested the potential role of ILCs, especially ILC2s, in spontaneous preterm labor, which is associated with brain damage and subsequent long-term neurodevelopmental deficits. Therefore, we hypothesized that ILCs, and especially ILC2s, play a role in preterm brain injury.C57Bl/6J mice at postnatal day 6 were subjected to hypoxia-ischemia (HI) insult induced by left carotid artery ligation and subsequent exposure to 10% oxygen in nitrogen. The presence of ILCs and ILC2s in the brain was examined at different time points after HI. The contribution of ILC2s to HI-induced preterm brain damage was explored using a conditionally targeted ILC2-deficient mouse strain (Rorα fl/fl IL7r Cre ), and gray and white-matter injury were evaluated at 7 days post-HI. The inflammatory response in the injured brain was assessed using immunoassays and immunochemistry staining.Significant increases in ILCs and ILC2s were observed at 24 h, 3 days, and 7 days post-HI in the injured brain hemisphere compared with the uninjured hemisphere in wild-type mice. ILC2s in the brain were predominantly located in the meninges of the injured ipsilateral hemispheres after HI but not in the brain parenchyma. Overall, we did not observe changes in cytokine/chemokine levels in the brains of Rorα fl/fl IL7r Cre mice compared with wild type animals apart from IL-13. Gray and white-matter tissue loss in the brain was not affected after HI in Rorα fl/fl IL7r Cre mice. Correspondingly, we did not find any differences in reactive microglia and astrocyte numbers in the brain in Rorα fl/fl IL7r Cre mice compared with wild-type mice following HI insult.After HI, ILCs and ILC2s accumulate in the injured brain hemisphere. However, ILC2s do not contribute to the development of brain damage in this mouse model of preterm brain injury.
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