Refine
Year of publication
- 2021 (3) (remove)
Document Type
- Article (3)
Language
- English (3)
Has Fulltext
- yes (3)
Is part of the Bibliography
- no (3)
Keywords
- Genetics (1)
- Immunogenetics (1)
- Immunology (1)
- Psychiatric disorders (1)
- calcitriol (1)
- glioblastoma (1)
- glioblastoma stem-like cells (1)
- vitamin D3 (1)
Institute
- Medizin (2)
Background: Biosurfactants are surface-active molecules produced by different microorganisms and display a promising alternative to synthetically derived food emulsifiers. One of these biosurfactants, synthesized by Bacillus subtilis, is the lipopeptide surfactin, which composes a linear fatty acid and cyclic peptide moiety. This study explores the interfacial and emulsion forming properties of surfactin to further characterize its suitability as an O/W emulsifier in food formulations.
Results: Surfactin revealed a high interfacial activity with a reduction of interfacial tension of 83.26 % to 4.21 ± 0.11 mN/m. O/W emulsions (coil = 10 % w/w) were prepared by high-pressure homogenization, which yielded volume-based mean particle sizes below 1 μm already at low emulsifier concentrations of 0.01 % (w/w). Environmental stress experiments revealed that emulsions were stable between pH 6 to pH 9. Furthermore, neither phase separation nor extensive emulsion instability was observed with NaCl addition up to 0.5 M. However, CaCl2 addition (> 3 mM) destabilized surfactin mediated emulsions. Finally, the main emulsion forming and stabilization effect of surfactin was related to its high interfacial activity and the high degree of electrostatic repulsion between the oil droplets (i.e. zeta-potential of up to −100 mV).
Conclusion; In comparison to other natural and synthetic emulsifiers, the results showed that surfactin is a strong candidate to form and stabilize O/W emulsions under the reported conditions.
Glioblastoma (GBM) is the most common and most aggressive primary brain tumor, with a very high rate of recurrence and a median survival of 15 months after diagnosis. Abundant evidence suggests that a certain sub-population of cancer cells harbors a stem-like phenotype and is likely responsible for disease recurrence, treatment resistance and potentially even for the infiltrative growth of GBM. GBM incidence has been negatively correlated with the serum levels of 25-hydroxy-vitamin D3, while the low pH within tumors has been shown to promote the expression of the vitamin D3-degrading enzyme 24-hydroxylase, encoded by the CYP24A1 gene. Therefore, we hypothesized that calcitriol can specifically target stem-like glioblastoma cells and induce their differentiation. Here, we show, using in vitro limiting dilution assays, quantitative real-time PCR, quantitative proteomics and ex vivo adult organotypic brain slice transplantation cultures, that therapeutic doses of calcitriol, the hormonally active form of vitamin D3, reduce stemness to varying extents in a panel of investigated GSC lines, and that it effectively hinders tumor growth of responding GSCs ex vivo. We further show that calcitriol synergizes with Temozolomide ex vivo to completely eliminate some GSC tumors. These findings indicate that calcitriol carries potential as an adjuvant therapy for a subgroup of GBM patients and should be analyzed in more detail in follow-up studies.
HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
(2021)
Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.