| 1. |
- Barregård, Lars, 1948, et al.
(författare)
-
Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine
- 2013
-
Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 18:18, s. 2377-2391
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.
|
|
| 2. |
- Borrega, M., et al.
(författare)
-
Utilizing and Valorizing Oat and Barley Straw as an Alternative Source of Lignocellulosic Fibers
- 2022
-
Ingår i: Materials. - : MDPI AG. - 1996-1944. ; 15:21
-
Tidskriftsartikel (refereegranskat)abstract
- The transition to sustainable, biodegradable, and recyclable materials requires new sources of cellulose fibers that are already used in large volumes by forest industries. Oat and barley straws provide interesting alternatives to wood fibers in lightweight material applications because of their similar chemical composition. Here we investigate processing and material forming concepts, which would enable strong fiber network structures for various applications. The idea is to apply mild pretreatment processing that could be distributed locally so that the logistics of the raw material collection could be made efficient. The actual material production would then combine foam-forming and hot-pressing operations that allow using all fractions of fiber materials with minimal waste. We aimed to study the technical features of this type of processing on a laboratory scale. The homogeneity of the sheet samples was very much affected by whether the raw material was mechanically refined or not. Straw fibers did not form a bond spontaneously with one another after drying the sheets, but their effective bonding required a subsequent hot pressing operation. The mechanical properties of the formed materials were at a similar level as those of the conventional wood-fiber webs. In addition to the technical aspects of materials, we also discuss the business opportunities and system-level requirements of using straw as an alternative source of lignocellulosic fibers.
|
|
| 3. |
|
|
| 4. |
- Ma, Haixia, et al.
(författare)
-
The transcription factor Foxp1 regulates aerobic glycolysis in adipocytes and myocytes
- 2023
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 299:6
-
Tidskriftsartikel (refereegranskat)abstract
- In recent years, lactate has been recognized as an important circulating energy substrate rather than only a dead-end metabolic waste product generated during glucose oxidation at low levels of oxygen. The term "aerobic glycolysis" has been coined to denote increased glucose uptake and lactate pro-duction despite normal oxygen levels and functional mito-chondria. Hence, in "aerobic glycolysis," lactate production is a metabolic choice, whereas in "anaerobic glycolysis," it is a metabolic necessity based on inadequate levels of oxygen. Interestingly, lactate can be taken up by cells and oxidized to pyruvate and thus constitutes a source of pyruvate that is in-dependent of insulin. Here, we show that the transcription factor Foxp1 regulates glucose uptake and lactate production in adipocytes and myocytes. Overexpression of Foxp1 leads to increased glucose uptake and lactate production. In addition, protein levels of several enzymes in the glycolytic pathway are upregulated, such as hexokinase 2, phosphofructokinase, aldolase, and lactate dehydrogenase. Using chromatin immu-noprecipitation and real-time quantitative PCR assays, we demonstrate that Foxp1 directly interacts with promoter consensus cis-elements that regulate expression of several of these target genes. Conversely, knockdown of Foxp1 suppresses these enzyme levels and lowers glucose uptake and lactate production. Moreover, mice with a targeted deletion of Foxp1 in muscle display systemic glucose intolerance with decreased muscle glucose uptake. In primary human adipocytes with induced expression of Foxp1, we find increased glycolysis and glycolytic capacity. Our results indicate Foxp1 may play an important role as a regulator of aerobic glycolysis in adipose tissue and muscle.
|
|
| 5. |
- Petkevicius, K., et al.
(författare)
-
TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis
- 2022
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- The regulation of cellular phosphatidylethanolamine (PE) acyl chain composition is poorly understood. Here, the authors show that TLCD1 and TLCD2 proteins mediate the formation of monounsaturated fatty acid-containing PE species and promote the progression of non-alcoholic steatohepatitis. The fatty acid composition of phosphatidylethanolamine (PE) determines cellular metabolism, oxidative stress, and inflammation. However, our understanding of how cells regulate PE composition is limited. Here, we identify a genetic locus on mouse chromosome 11, containing two poorly characterized genes Tlcd1 and Tlcd2, that strongly influences PE composition. We generated Tlcd1/2 double-knockout (DKO) mice and found that they have reduced levels of hepatic monounsaturated fatty acid (MUFA)-containing PE species. Mechanistically, TLCD1/2 proteins act cell intrinsically to promote the incorporation of MUFAs into PEs. Furthermore, TLCD1/2 interact with the mitochondria in an evolutionarily conserved manner and regulate mitochondrial PE composition. Lastly, we demonstrate the biological relevance of our findings in dietary models of metabolic disease, where Tlcd1/2 DKO mice display attenuated development of non-alcoholic steatohepatitis compared to controls. Overall, we identify TLCD1/2 proteins as key regulators of cellular PE composition, with our findings having broad implications in understanding and treating disease.
|
|
| 6. |
- Ruiz, Mario, 1984, et al.
(författare)
-
Evolutionarily conserved long-chain Acyl-CoA synthetases regulate membrane composition and fluidity
- 2019
-
Ingår i: Elife. - 2050-084X. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- The human AdipoR1 and AdipoR2 proteins, as well as their C. elegans homolog PAQR-2, protect against cell membrane rigidification by exogenous saturated fatty acids by regulating phospholipid composition. Here, we show that mutations in the C. elegans gene acs-13 help to suppress the phenotypes of paqr-2 mutant worms, including their characteristic membrane fluidity defects. acs-13 encodes a homolog of the human acyl-CoA synthetase ACSL1, and localizes to the mitochondrial membrane where it likely activates long chains fatty acids for import and degradation. Using siRNA combined with lipidomics and membrane fluidity assays (FRAP and Laurdan dye staining) we further show that the human ACSL1 potentiates lipotoxicity by the saturated fatty acid palmitate: silencing ACSL1 protects against the membrane rigidifying effects of palmitate and acts as a suppressor of AdipoR2 knockdown, thus echoing the C. elegans findings. We conclude that acs-13 mutations in C. elegans and ACSL1 knockdown in human cells prevent lipotoxicity by promoting increased levels of polyunsaturated fatty acid-containing phospholipids.
|
|
| 7. |
- Ruiz, Mario, 1984, et al.
(författare)
-
Extensive transcription mis-regulation and membrane defects in AdipoR2-deficient cells challenged with saturated fatty acids
- 2021
-
Ingår i: Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids. - : Elsevier BV. - 1388-1981. ; 1866:4
-
Tidskriftsartikel (refereegranskat)abstract
- How cells maintain vital membrane lipid homeostasis while obtaining most of their constituent fatty acids from a varied diet remains largely unknown. Here, we used transcriptomics, lipidomics, growth and respiration assays, and membrane property analyses in human HEK293 cells or human umbilical vein endothelial cells (HUVEC) to show that the function of AdipoR2 is to respond to membrane rigidification by regulating many lipid metabolism genes. We also show that AdipoR2-dependent membrane homeostasis is critical for growth and respiration in cells challenged with saturated fatty acids. Additionally, we found that AdipoR2 deficiency causes transcriptome and cell physiological defects similar to those observed in SREBP-deficient cells upon SFA challenge. Finally, we compared several genes considered important for lipid homeostasis, namely AdipoR2, SCD, FADS2, PEMT and ACSL4, and found that AdipoR2 and SCD are the most important among these to prevent membrane rigidification and excess saturation when human cells are challenged with exogenous SFAs. We conclude that AdipoR2-dependent membrane homeostasis is one of the primary mechanisms that protects against exogenous SFAs.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
