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  • 1
    Online Resource
    Online Resource
    Accumulation of cholesterol, triglycerides and ceramides in hepatocellular carcinomas of diethylnitrosamine injected mice
    Springer Science and Business Media LLC ; 2021
    In:  Lipids in Health and Disease Vol. 20, No. 1 ( 2021-12)
    Details
    In: Lipids in Health and Disease, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2021-12)
    Abstract: Dysregulated lipid metabolism is critically involved in the development of hepatocellular carcinoma (HCC). The respective metabolic pathways affected in HCC can be identified using suitable experimental models. Mice injected with diethylnitrosamine (DEN) and fed a normal chow develop HCC. For the analysis of the pathophysiology of HCC in this model a comprehensive lipidomic analysis was performed. Methods Lipids were measured in tumor and non-tumorous tissues by direct flow injection analysis. Proteins with a role in lipid metabolism were analysed by immunoblot. Mann-Whitney U-test or paired Student´s t-test were used for data analysis. Results Intra-tumor lipid deposition is a characteristic of HCCs, and di- and triglycerides accumulated in the tumor tissues of the mice. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha, lipoprotein lipase and hepatic lipase protein were low in the tumors whereas proteins involved in de novo lipogenesis were not changed. Higher rates of de novo lipogenesis cause a shift towards saturated acyl chains, which did not occur in the murine HCC model. Besides, LDL-receptor protein and cholesteryl ester levels were higher in the murine HCC tissues. Ceramides are cytotoxic lipids and are low in human HCCs. Notably, ceramide levels increased in the murine tumors, and the simultaneous decline of sphingomyelins suggests that sphingomyelinases were involved herein. DEN is well described to induce the tumor suppressor protein p53 in the liver, and p53 was additionally upregulated in the tumors. Conclusions Ceramides mediate the anti-cancer effects of different chemotherapeutic drugs and restoration of ceramide levels was effective against HCC. High ceramide levels in the tumors makes the DEN injected mice an unsuitable model to study therapies targeting ceramide metabolism. This model is useful for investigating how tumors evade the cytotoxic effects of ceramides.
    Type of Medium: Online Resource
    ISSN: 1476-511X
    URL: Article
    DOI: 10.1186/s12944-021-01567-w
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2091381-3
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  • 2
    Online Resource
    Online Resource
    Genotype–phenotype associations of polymorphisms within the gene locus of NOD-like receptor pyrin domain containing 3 in Swiss inflammatory bowel disease patients
    Springer Science and Business Media LLC ; 2021
    In:  BMC Gastroenterology Vol. 21, No. 1 ( 2021-08-03)
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    In: BMC Gastroenterology, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2021-08-03)
    Abstract: Genetic variations within the regulatory region of the gene encoding NOD-like receptor pyrin domain containing 3 ( NLRP3 ) have been associated with Crohn’s Disease (CD). NLRP3 is part of the NLRP3-inflammasome that mediates the maturation of IL-1β and IL-18. Carrying the major allele of the single nucleotide polymorphisms (SNPs) rs10733113, rs4353135 and rs55646866 is associated with an increased risk for CD. We here studied the impact of these polymorphisms on clinical characteristics in patients of the Swiss IBD Cohort Study (SIBDCS). Methods We included 981 Crohn’s disease (CD) patients and 690 ulcerative colitis (UC) patients of the SIBDCS. We analyzed whether three CD-associated NLRP3 polymorphisms have an impact on the clinical disease course in these patients. Results In CD patients presence of the major allele (G) of rs10733113 was associated with less surgeries and lower maximal CDAI and a similar trend was observed for rs55646866 and rs4353135. Presence of the major allele of all three SNPs was negatively correlated to maximal CDAI. In UC patients homozygous genotype for the major allele (CC) for rs55646866 was associated with a higher age at diagnosis and a higher MTWAI index. Homozygous genotype for the major allele of all three polymorphisms was associated with a higher number of ambulatory visits and longer hospital stays. Conclusions In CD patients presence of the major allele of all three polymorphisms was associated with markers of a less severe disease course, while in UC the homozygous genotype for all major alleles suggested a more severe disease activity.
    Type of Medium: Online Resource
    ISSN: 1471-230X
    URL: Article
    DOI: 10.1186/s12876-021-01880-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2041351-8
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  • 3
    Online Resource
    Online Resource
    Effects of anti-TNF therapy and immunomodulators on anxiety and depressive symptoms in patients with inflammatory bowel disease: a 5-year analysis
    SAGE Publications ; 2021
    In:  Therapeutic Advances in Gastroenterology Vol. 14 ( 2021-01), p. 175628482110337-
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    In: Therapeutic Advances in Gastroenterology, SAGE Publications, Vol. 14 ( 2021-01), p. 175628482110337-
    Abstract: Anxiety and depression are prevalent in patients with inflammatory bowel diseases (IBD), especially during IBD flares. IBD therapies can profoundly affect the mood of patients with IBD. We aimed to determine the long-term impact of anti-tumor necrosis factor (anti-TNF) and immunomodulators (IM) on anxiety and depressive symptoms in IBD patients. Methods: We compared three treatment groups with IM only (group A), anti-TNF ± IM (group B) and no such therapy (group C). Patients completed the hospital anxiety and depression scale (HADS) at 1 year, 3 years, and 5 years after start of treatment. Results: In total, 581 patients with IBD (42.9% Crohn’s disease, 57.1% ulcerative colitis/IBD unclassified) participated in this study. Effects of treatment were analyzed in a mixed effects model, with and without correction for confounders. Compared with group C, group B showed a significant treatment-related improvement in both anxiety and depressive symptoms within the first 2.5 years and also thereafter. Group A showed a significant long-term improvement of anxiety and both short-term and long-term improvement in depressive symptoms. The significance of these results was maintained after correction for confounders, including corticosteroid treatment. Additionally, both groups A and B showed a significant decrease in disease activity in the first 2.5 years after start of treatment and also thereafter. Anti-TNF and IM treatment were associated with a similarly significant decrease in anxiety and depressive symptoms over an observation period of up to 5 years. Conclusion: Besides a clear benefit for disease activity, anti-TNF and IM apparently improve the mood of patients with IBD.
    Type of Medium: Online Resource
    ISSN: 1756-2848 , 1756-2848
    URL: Article
    DOI: 10.1177/17562848211033763
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
    detail.hit.zdb_id: 2440710-0
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