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  • 1
    Online Resource
    Online Resource
    Contemporary Management of Severe Symptomatic Aortic Stenosis
    Elsevier BV ; 2021
    In:  Journal of the American College of Cardiology Vol. 78, No. 22 ( 2021-11), p. 2131-2143
    Details
    In: Journal of the American College of Cardiology, Elsevier BV, Vol. 78, No. 22 ( 2021-11), p. 2131-2143
    Type of Medium: Online Resource
    ISSN: 0735-1097
    URL: Article
    DOI: 10.1016/j.jacc.2021.09.864
    RVK:
    XA 17760
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 1468327-1
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  • 2
    Online Resource
    Online Resource
    Reduced Androgen Receptor Expression in Genital Skin Fibroblasts From Patients With 45,X/46,XY Mosaicism
    The Endocrine Society ; 2019
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 104, No. 10 ( 2019-10-01), p. 4630-4638
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 104, No. 10 ( 2019-10-01), p. 4630-4638
    Abstract: Molecular mechanisms causing the broad phenotypic diversity of external masculinization in individuals with 45,X/46,XY mosaicism are poorly understood. Objective Analysis of androgen receptor (AR) expression and function as a putative influencing factor for the genital phenotype in patients with 45,X/46,XY mosaicism. Design Measurement of AR mRNA expression levels, AR activity [DHT-mediated APOD (apolipoprotein D) induction] and cellular 45,X/46,XY ratios in genital skin fibroblasts from individuals with 45,X/46,XY mosaicism and male reference individuals, and determination of the external virilization scale from individuals with 45,X/46,XY mosaicism. Setting University hospital endocrine research laboratory. Patients or Other Participants: 30 genital skin fibroblast cultures (GFs) from male reference individuals and 15 GFs from individuals with 45,X/46,XY mosaicism. Intervention None Main Outcome Measures Determination of AR mRNA expression and AR activity in male reference GFs and 45,X/46,XY GFs and correlation of the obtained data with the cellular 45,X/46,XY ratios and the patients’ external virilization scale. Results In 6 of 15 45,X/46,XY GFs, AR mRNA expression and AR activity were significantly lower compared with those in the 46,XY reference GFs. In this subgroup of reduced AR mRNA expression, a positive trend was seen between AR mRNA expression and the percentage of XY-positive cells. Furthermore, we found a positive correlation between AR activity and the external virilization scale in the 15 45,X/46,XY GF samples (P = 0.03). Conclusion Our results suggest that AR expression and AR activity might influence the phenotypic variability seen in patients with 45,X/46,XY mosaicism.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/jc.2019-00108
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2019
    detail.hit.zdb_id: 2026217-6
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  • 3
    Online Resource
    Online Resource
    The relevance of tissue angiotensin-converting enzyme: manifestations in mechanistic and endpoint data
    Elsevier BV ; 2001
    In:  The American Journal of Cardiology Vol. 88, No. 9 ( 2001-11), p. 1-20
    Details
    In: The American Journal of Cardiology, Elsevier BV, Vol. 88, No. 9 ( 2001-11), p. 1-20
    Type of Medium: Online Resource
    ISSN: 0002-9149
    URL: Article
    DOI: 10.1016/S0002-9149(01)01878-1
    RVK:
    XA 18500
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2001
    detail.hit.zdb_id: 2019595-3
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  • 4
    Online Resource
    Online Resource
    HDAC2 Is Involved in the Regulation of BRN3A in Melanocytes and Melanoma
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 2 ( 2022-01-13), p. 849-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 2 ( 2022-01-13), p. 849-
    Abstract: The neural crest transcription factor BRN3A is essential for the proliferation and survival of melanoma cells. It is frequently expressed in melanoma but not in normal melanocytes or benign nevi. The mechanisms underlying the aberrant expression of BRN3A are unknown. Here, we investigated the epigenetic regulation of BRN3A in melanocytes and melanoma cell lines treated with DNA methyltransferase (DNMT), histone acetyltransferase (HAT), and histone deacetylase (HDAC) inhibitors. DNMT and HAT inhibition did not significantly alter BRN3A expression levels, whereas panHDAC inhibition by trichostatin A led to increased expression. Treatment with the isoform-specific HDAC inhibitor mocetinostat, but not with PCI-34051, also increased BRN3A expression levels, suggesting that class I HDACs HDAC1, HDAC2, and HDAC3, and class IV HDAC11, were involved in the regulation of BRN3A expression. Transient silencing of HDACs 1, 2, 3, and 11 by siRNAs revealed that, specifically, HDAC2 inhibition was able to increase BRN3A expression. ChIP-Seq analysis uncovered that HDAC2 inhibition specifically increased H3K27ac levels at a distal enhancer region of the BRN3A gene. Altogether, our data suggest that HDAC2 is a key epigenetic regulator of BRN3A in melanocytes and melanoma cells. These results highlight the importance of epigenetic mechanisms in regulating melanoma oncogenes.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23020849
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    The myelin protein PMP2 is regulated by SOX10 and drives melanoma cell invasion
    Wiley ; 2019
    In:  Pigment Cell & Melanoma Research Vol. 32, No. 3 ( 2019-05), p. 424-434
    Details
    In: Pigment Cell & Melanoma Research, Wiley, Vol. 32, No. 3 ( 2019-05), p. 424-434
    Abstract: The transcription factor sex determining region Y‐box 10 (SOX10) plays a key role in the development of melanocytes and glial cells from neural crest precursors. SOX10 is involved in melanoma initiation, proliferation, invasion, and survival. However, specific mediators which impart its oncogenic properties remain widely unknown. To identify target genes of SOX10, we performed RNA sequencing after ectopic expression of SOX10 in human melanoma cells. Among nine differentially regulated genes, peripheral myelin protein 2 ( PMP2 ) was consistently upregulated in several cell lines. Direct regulation of PMP2 by SOX10 was shown by chromatin immunoprecipitation, electrophoretic mobility shift, and luciferase reporter assays. Moreover, a coregulation of PMP2 by SOX10 and early growth response 2 in melanoma cells was found. Phenotypical investigation demonstrated that PMP2 expression can increase melanoma cell invasion. As PMP2 protein was detected only in a subset of melanoma cell lines, it might contribute to melanoma heterogeneity.
    Type of Medium: Online Resource
    ISSN: 1755-1471 , 1755-148X
    URL: Issue
    URL: Article
    DOI: 10.1111/pcmr.2019.32.issue-3
    DOI: 10.1111/pcmr.12760
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2425880-5
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  • 6
    Online Resource
    Online Resource
    Contribution of Selected Vitamins and Trace Elements to Immune Function
    S. Karger AG ; 2007
    In:  Annals of Nutrition and Metabolism Vol. 51, No. 4 ( 2007), p. 301-323
    Details
    In: Annals of Nutrition and Metabolism, S. Karger AG, Vol. 51, No. 4 ( 2007), p. 301-323
    Abstract: Adequate intakes of vitamins and trace elements are required for the immune system to function efficiently. Micronutrient deficiency suppresses immune functions by affecting the innate T-cell-mediated immune response and adaptive antibody response, and leads to dysregulation of the balanced host response. This increases the susceptibility to infections, with increased morbidity and mortality. In turn, infections aggravate micronutrient deficiencies by reducing nutrient intake, increasing losses, and interfering with utilization by altering metabolic pathways. Insufficient intake of micronutrients occurs in people with eating disorders, in smokers (both active and passive), in individuals with chronic alcohol abuse, in patients with certain diseases, during pregnancy and lactation, and in the elderly. With aging a variety of changes are observed in the immune system, which translate into less effective innate and adaptive immune responses and increased susceptibility to infections. Antioxidant vitamins and trace elements (vitamins C, E, selenium, copper, and zinc) counteract potential damage caused by reactive oxygen species to cellular tissues and modulate immune cell function through regulation of redox-sensitive transcription factors and affect production of cytokines and prostaglandins. Adequate intake of vitamins B 〈 sub 〉 6 〈 /sub 〉 , folate, B 〈 sub 〉 12 〈 /sub 〉 , C, E, and of selenium, zinc, copper, and iron supports a Th1 cytokine-mediated immune response with sufficient production of proinflammatory cytokines, which maintains an effective immune response and avoids a shift to an anti-inflammatory Th2 cell-mediated immune response and an increased risk of extracellular infections. Supplementation with these micronutrients reverses the Th2 cell-mediated immune response to a proinflammatory Th1 cytokine-regulated response with enhanced innate immunity. Vitamins A and D play important roles in both cell-mediated and humoral antibody response and support a Th2-mediated anti-inflammatory cytokine profile. Vitamin A deficiency impairs both innate immunity (mucosal epithelial regeneration) and adaptive immune response to infection resulting in an impaired ability to counteract extracellular pathogens. Vitamin D deficiency is correlated with a higher susceptibility to infections due to impaired localized innate immunity and defects in antigen-specific cellular immune response. Overall, inadequate intake and status of these vitamins and minerals may lead to suppressed immunity, which predisposes to infections and aggravates malnutrition.
    Type of Medium: Online Resource
    ISSN: 0250-6807 , 1421-9697
    URL: Article
    DOI: 10.1159/000107673
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2007
    detail.hit.zdb_id: 1481977-6
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  • 7
    Online Resource
    Online Resource
    Inhibition of histone deacetylases in melanoma—a perspective from bench to bedside
    Wiley ; 2016
    In:  Experimental Dermatology Vol. 25, No. 11 ( 2016-11), p. 831-838
    Details
    In: Experimental Dermatology, Wiley, Vol. 25, No. 11 ( 2016-11), p. 831-838
    Abstract: Histone deacetylases (HDACs) are critically involved in epigenetic gene regulation through alterations of the chromatin status of DNA. Aberrant expression, dysregulation of their enzymatic activity or imbalances between HDACs and histone acetyltransferases are likely involved in the development and progression of cancer. Pharmacologic inhibition of HDACs shows potent antitumor activity in a panel of malignancies such as colon or gastric cancer and multiple myeloma. In this review, we summarize the current knowledge of HDACs in melanoma and evaluate the application of HDAC inhibition from an experimental and clinical perspective. The molecular functions of HDACs can be classified into histone and non‐histone effects with diverse implications in proliferation, cell cycle progression and apoptosis. HDAC inhibition results in G1 cell cycle arrest, induces apoptosis and increases the immunogenicity of melanoma cells. Some studies proposed that HDAC inhibition may overcome the resistance of melanoma cells to BRAF inhibition. Several inhibitors such as vorinostat, entinostat and valproic acid have recently been tested in phase I and early phase II trials, yet most agents show limited efficacy and tolerability as single agents. The most frequent adverse events of HDAC inhibition comprise haematological toxicity, fatigue, nausea and laboratory abnormalities. Existing evidence supports the hypothesis that HDAC inhibitors (HDACi) may sensitize melanoma cells to immunotherapy and targeted therapy and hence bear therapeutic potential concurrent with immune checkpoint blockade or BRAF and MEK inhibition.
    Type of Medium: Online Resource
    ISSN: 0906-6705 , 1600-0625
    URL: Issue
    URL: Article
    DOI: 10.1111/exd.2016.25.issue-11
    DOI: 10.1111/exd.13089
    RVK:
    XA 42446
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2026228-0
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  • 8
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    Online Resource
    The oxidative potential of differently charged silver and gold nanoparticles on three human lung epithelial cell types
    Springer Science and Business Media LLC ; 2015
    In:  Journal of Nanobiotechnology Vol. 13, No. 1 ( 2015-12)
    Details
    In: Journal of Nanobiotechnology, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2015-12)
    Type of Medium: Online Resource
    ISSN: 1477-3155
    URL: Article
    DOI: 10.1186/s12951-014-0062-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2015
    detail.hit.zdb_id: 2100022-0
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  • 9
    Online Resource
    Online Resource
    Selected vitamins and trace elements support immune function by strengthening epithelial barriers and cellular and humoral immune responses
    Cambridge University Press (CUP) ; 2007
    In:  British Journal of Nutrition Vol. 98, No. S1 ( 2007-10), p. S29-S35
    Details
    In: British Journal of Nutrition, Cambridge University Press (CUP), Vol. 98, No. S1 ( 2007-10), p. S29-S35
    Abstract: Adequate intakes of micronutrients are required for the immune system to function efficiently. Micronutrient deficiency suppresses immunity by affecting innate, T cell mediated and adaptive antibody responses, leading to dysregulation of the balanced host response. This situation increases susceptibility to infections, with increased morbidity and mortality. In turn, infections aggravate micronutrient deficiencies by reducing nutrient intake, increasing losses, and interfering with utilization by altering metabolic pathways. Insufficient intake of micronutrients occurs in people with eating disorders, in smokers (active and passive), in individuals with chronic alcohol abuse, in certain diseases, during pregnancy and lactation, and in the elderly. This paper summarises the roles of selected vitamins and trace elements in immune function. Micronutrients contribute to the body's natural defences on three levels by supporting physical barriers (skin/mucosa), cellular immunity and antibody production. Vitamins A, C, E and the trace element zinc assist in enhancing the skin barrier function. The vitamins A, B 6 , B 12 , C, D, E and folic acid and the trace elements iron, zinc, copper and selenium work in synergy to support the protective activities of the immune cells. Finally, all these micronutrients, with the exception of vitamin C and iron, are essential for antibody production. Overall, inadequate intake and status of these vitamins and trace elements may lead to suppressed immunity, which predisposes to infections and aggravates malnutrition. Therefore, supplementation with these selected micronutrients can support the body's natural defence system by enhancing all three levels of immunity.
    Type of Medium: Online Resource
    ISSN: 0007-1145 , 1475-2662
    URL: Article
    DOI: 10.1017/S0007114507832971
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2007
    detail.hit.zdb_id: 2016047-1
    SSG: 12
    SSG: 21
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  • 10
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    Online Resource
    Immune-Enhancing Role of Vitamin C and Zinc and Effect on Clinical Conditions
    S. Karger AG ; 2006
    In:  Annals of Nutrition and Metabolism Vol. 50, No. 2 ( 2006), p. 85-94
    Details
    In: Annals of Nutrition and Metabolism, S. Karger AG, Vol. 50, No. 2 ( 2006), p. 85-94
    Abstract: Vitamin C concentrations in the plasma and leukocytes rapidly decline during infections and stress. Supplementation of vitamin C was found to improve components of the human immune system such as antimicrobial and natural killer cell activities, lymphocyte proliferation, chemotaxis, and delayed-type hypersensitivity. Vitamin C contributes to maintaining the redox integrity of cells and thereby protects them against reactive oxygen species generated during the respiratory burst and in the inflammatory response. Likewise, zinc undernutrition or deficiency was shown to impair cellular mediators of innate immunity such as phagocytosis, natural killer cell activity, and the generation of oxidative burst. Therefore, both nutrients play important roles in immune function and the modulation of host resistance to infectious agents, reducing the risk, severity, and duration of infectious diseases. This is of special importance in populations in which insufficient intake of these nutrients is prevalent. In the developing world, this is the case in low- and middle-income countries, but also in subpopulations in industrialized countries, e.g. in the elderly. A large number of randomized controlled intervention trials with intakes of up to 1 g of vitamin C and up to 30 mg of zinc are available. These trials document that adequate intakes of vitamin C and zinc ameliorate symptoms and shorten the duration of respiratory tract infections including the common cold. Furthermore, vitamin C and zinc reduce the incidence and improve the outcome of pneumonia, malaria, and diarrhea infections, especially in children in developing countries.
    Type of Medium: Online Resource
    ISSN: 0250-6807 , 1421-9697
    URL: Article
    DOI: 10.1159/000090495
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2006
    detail.hit.zdb_id: 1481977-6
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