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  • Oxford University Press (OUP)  (5)
  • 1
    In: Inflammatory Bowel Diseases, Oxford University Press (OUP), Vol. 28, No. 6 ( 2022-06-03), p. 923-935
    Kurzfassung: Intestinal fibrosis is a common complication of Crohn’s disease (CD) and is characterized by the excessive accumulation of extracellular matrix produced by activated myofibroblasts. Caveolin-1 (CAV1) inhibits fibrosis. However, limited data show that CAV1 affects intestinal fibrosis. Methods Human CD tissue samples were gained from patients with CD who underwent surgical resection of the intestine and were defined as stenotic or nonstenotic areas. A dextran sodium sulfate–induced mouse model of intestinal fibrosis was established. For in vitro experiments, we purchased CCD-18Co intestinal fibrosis cells and isolated and cultured human primary colonic fibroblasts. These fibroblasts were activated by transforming growth factor β administration for 48 hours. In the functional experiments, a specific small interfering RNA or overexpression plasmid was transfected into fibroblasts. The messenger RNA levels of fibrosis markers, such as α-smooth muscle actin, fibronectin, connective tissue growth factor, and collagen I1α, were determined using quantitative polymerase chain reaction. Western blot analysis was applied to detect the expression of CAV1, SQSTM1/p62 (sequestosome 1), and other fibrosis markers. Results In human CD samples and the dextran sodium sulfate–induced mouse model of intestinal fibrosis, we observed a downregulation of CAV1 in fibrosis-activated areas. Mechanistically, CAV1 knockdown in both human primary colonic fibroblasts and CCD-18Co cells promoted fibroblast activation, while CAV1 overexpression inhibited fibroblast activation in vitro. We found that SQSTM1/p62 positively correlated with CAV1 expression levels in patients with CD and that it was indirectly modulated by CAV1 expression. Rescue experiments showed that CAV1 decreased primary human intestinal fibroblast activation by inhibiting fibroblast autophagy through the modulation of SQSTM1/p62. Conclusions Our data demonstrate that CAV1 deficiency induces fibroblast activation by indirectly regulating SQSTM1/p62 to promote fibroblast autophagy. CAV1 or SQSTM1/p62 may be potential therapeutic targets for intestinal fibrosis.
    Materialart: Online-Ressource
    ISSN: 1078-0998 , 1536-4844
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2022
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    Online-Ressource
    Online-Ressource
    Oxford University Press (OUP) ; 2021
    In:  Monthly Notices of the Royal Astronomical Society
    In: Monthly Notices of the Royal Astronomical Society, Oxford University Press (OUP)
    Kurzfassung: The accurate line strengths, transition rates, oscillator strengths, and lifetimes from the inner-shell 2s2p2(4P)3s states 5P and 3P of N II are reported within the framework of the multiconfiguration Dirac-Hartree-Fock (MCDHF) method. The effects of core-core, core-valence, and valence correlations; the Breit interaction; and QED effect are taken into account. Through investigating the influences of electron correlation effects on the quintet states, it is found that the core correlation effect has certain compensation effect in accurately optimizing the line strengths, transition rates and lifetimes of quintet states; the branching fractions of 2s2p3 5S$^\circ _{2}$–2s2p2(4P)3s 5P1, 2, 3 tend to 1, which is inferred as a peculiar intrinsic property that can be useful for plasma diagnostics; unlike 3P0, 1, 2 and 5P1, 3, the calculations of lifetime of 5P2 show some J-dependence, and the velocity form calculations for this J=2-dependence are much more sensitive to electron correlations of 1s22s2p2(4P)3l (l = p, d) than those in the length gauge, which will be helpful to deal with the calculations of lifetime with J=2-dependence in the carbon like isoelectronic series.
    Materialart: Online-Ressource
    ISSN: 0035-8711 , 1365-2966
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2021
    ZDB Id: 2016084-7
    SSG: 16,12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: Brain, Oxford University Press (OUP), Vol. 146, No. 4 ( 2023-04-19), p. 1420-1435
    Kurzfassung: Sphingolipids are a diverse family of lipids with critical structural and signalling functions in the mammalian nervous system, where they are abundant in myelin membranes. Serine palmitoyltransferase, the enzyme that catalyses the rate-limiting reaction of sphingolipid synthesis, is composed of multiple subunits including an activating subunit, SPTSSA. Sphingolipids are both essential and cytotoxic and their synthesis must therefore be tightly regulated. Key to the homeostatic regulation are the ORMDL proteins that are bound to serine palmitoyltransferase and mediate feedback inhibition of enzymatic activity when sphingolipid levels become excessive. Exome sequencing identified potential disease-causing variants in SPTSSA in three children presenting with a complex form of hereditary spastic paraplegia. The effect of these variants on the catalytic activity and homeostatic regulation of serine palmitoyltransferase was investigated in human embryonic kidney cells, patient fibroblasts and Drosophila. Our results showed that two different pathogenic variants in SPTSSA caused a hereditary spastic paraplegia resulting in progressive motor disturbance with variable sensorineural hearing loss and language/cognitive dysfunction in three individuals. The variants in SPTSSA impaired the negative regulation of serine palmitoyltransferase by ORMDLs leading to excessive sphingolipid synthesis based on biochemical studies and in vivo studies in Drosophila. These findings support the pathogenicity of the SPTSSA variants and point to excessive sphingolipid synthesis due to impaired homeostatic regulation of serine palmitoyltransferase as responsible for defects in early brain development and function.
    Materialart: Online-Ressource
    ISSN: 0006-8950 , 1460-2156
    RVK:
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2023
    ZDB Id: 1474117-9
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: Virus Evolution, Oxford University Press (OUP), Vol. 7, No. 1 ( 2021-01-20)
    Kurzfassung: Trillions of viruses inhabit the gastrointestinal tract. Some of them have been well-studied on their roles in infection and human health, but the majority remains unsurveyed. It has been established that the composition of the gut virome is highly variable based on the changes of diet, physical state, and environmental factors. However, the effect of host genetic factors, for example ethnic origin, on the gut virome is rarely investigated. Here, we characterized and compared the gut virome in a cohort of local Chinese residents and visiting Pakistani individuals, each group containing twenty-four healthy adults and six children. Using metagenomic shotgun sequencing and assembly of fecal samples, a huge number of viral operational taxonomic units (vOTUs) were identified for profiling the DNA and RNA viromes. National background contributed a primary variation to individuals’ gut virome. Compared with the Chinese adults, the Pakistan adults showed higher macrodiversity and different compositional and functional structures in their DNA virome and lower diversity and altered composition in their RNA virome. The virome variations of Pakistan children were not only inherited from that of the adults but also tended to share similar characteristics with the Chinese cohort. We also analyzed and compared the bacterial microbiome between two cohorts and further revealed numerous connections between viruses and bacterial host. Statistically, the gut DNA and RNA viromes were covariant to some extent (P  & lt; 0.001), and they both correlated the holistic bacterial composition and vice versa. This study provides an overview of the gut viral community in Chinese and visiting Pakistanis and proposes a considerable role of ethnic origin in shaping the virome.
    Materialart: Online-Ressource
    ISSN: 2057-1577
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2021
    ZDB Id: 2818949-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    In: FEMS Yeast Research, Oxford University Press (OUP), Vol. 21, No. 3 ( 2021-04-07)
    Kurzfassung: Amphotericin B (AmB) is a very effective antifungal agent, and resistance in clinical isolates is rare. However, clinical treatment with AmB is often associated with severe side effects. Reducing the administration dose of AmB by combining it with other agents is a promising strategy to minimize this toxicity. In this study, we screened a small compound library and observed that the anti-obesity drug rimonabant exhibited synergistic antifungal action with AmB against Candida species and Cryptococcus neoformans. Moreover, the combination of AmB and rimonabant exhibited synergistic or additive effects against Candida albicans biofilm formation and cell viability in preformed biofilms. The effects of this combination were further confirmed in vivo using a murine systemic infection model. Exploration of the mechanism of synergy revealed that rimonabant enhances the fungicidal activity of AmB by increasing cellular oxidative stress and cell membrane permeability. These findings provide a foundation for the possible development of AmB–rimonabant polytherapies for fungal infections.
    Materialart: Online-Ressource
    ISSN: 1567-1356 , 1567-1364
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2021
    ZDB Id: 2052068-2
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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