المؤلفون: Hess, Jamila, Barysch-Bonderer, Marjam-Jeanette, Seeli, Corsin, Laube, Julia, Ghosh, Adhideb, id_orcid:0 000-0002-5160-4571, Deinsberger, Julia, Weber, Benedikt, Hafner, Jürg, Meier-Schiesser, Barbara

المصدر: Acta dermato-venereologica, 104

مصطلحات موضوعية: Martorell hypertensive ischaemic leg ulcer, inflammation, STAC2

الوصف: Martorell hypertensive ischaemic leg ulcer (Martorell HYTILU) is a rare but significant cause of distal leg ulcers. Although hypertension and diabetes are known factors in its development, the precise pathogenesis of Martorell HYTILU remains elusive. To reach a better understanding of Martorell HYTILU, transcriptomic analysis was conducted through RNA sequencing and immunohistochemical comparison of Martorell HYTILU (n = 17) with chronic venous ulcers (n = 4) and healthy skin (n = 4). Gene expression analysis showed a marked activation of immune-related pathways in both Martorell HYTILU and chronic venous ulcers compared with healthy skin. Notably, neutrophil activity was substantially higher in Martorell HYTILU. While pathway analysis revealed a mild downregulation of several immune pathways in Martorell HYTILU compared with chronic venous ulcers, keratinization, cornification, and epidermis development were significantly upregulated in Martorell HYTILU. Additionally, STAC2, a gene encoding for a protein promoting the expression of the calcium channel Cav1.1, was significantly upregulated in Martorell HYTILU and was detected perivascularly in situ (Martorell HYTILU n = 24; chronic venous ulcers n = 9, healthy skin n = 11). The high expression of STAC2 in Martorell HYTILU suggests that increased calcium influx plays an important role in the pathogenesis of the disease. Consequently, calcium channel antagonists could be a promising treatment avenue for Martorell HYTILU.

وصف الملف: application/application/pdf

العلاقة: http://hdl.handle.net/20.500.11850/677308Test

الإتاحة: https://doi.org/20.500.11850/67730810.3929/ethz-b-00067730810.2340/actadv.v104.40090Test
https://hdl.handle.net/20.500.11850/677308Test

المؤلفون: Sachs, David, Jakob, Raphael, Restivo, Gaetana, Hafner, Jürg, Lindenblatt, Nicole, Ehret, Alexander Edmund, id_orcid:0 000-0002-8740-8900, Mazza, Edoardo, id_orcid:0 000-0001-9427-4157

المصدر: Biomechanics and Modeling in Mechanobiology

مصطلحات موضوعية: Dermis, Mechanobiology, Electrical potential, Osmotic pressure, Quadriphasic model

الوصف: The present study investigates the multiphasic nature of the mechanical behavior of human dermis. Motivated by experimental observations and by consideration of its composition, a quadriphasic model of the dermis is proposed, distinguishing solid matrix components, interstitial fluid and charged constituents moving within the fluid, i.e., anions and cations. Compression and tensile experiments with and without change of osmolarity of the bath are performed to characterize the chemo-mechanical coupling in the dermis. Model parameters are determined through inverse analysis. The computations predict a dominant role of the permeability in the determination of the temporal evolution of the mechanical response of the tissue. In line with the previous studies on other tissues, the analysis shows that an ideal model based on Donnan's equilibrium overestimates the osmotic pressure in skin for the case of very dilute solutions. The quadriphasic model is applied to predict changes in dermal cell environment and therefore alterations in what is called the "mechanome," associated with skin stretch. The simulations indicate that skin deformation causes a variation in several local variables, including in particular the electric field associated with a deformation-induced non-homogeneous distribution of fixed charges. ; ISSN:1617-7959 ; ISSN:1617-7940

وصف الملف: application/application/pdf

العلاقة: info:eu-repo/semantics/altIdentifier/wos/001185760600002; http://hdl.handle.net/20.500.11850/667314Test

الإتاحة: https://doi.org/20.500.11850/667314Test
https://doi.org/10.3929/ethz-b-000667314Test
https://doi.org/10.1007/s10237-024-01827-5Test
https://hdl.handle.net/20.500.11850/667314Test

المؤلفون: Richter, Clara, Hafner, Jürg, Schuermann, Manuel, Tanadini, Matteo, Trisconi, Nisia, Schmid-Grendelmeier, Peter, Kündig, Thomas, Nägeli, Mirjam, Brüggen, Marie-Charlotte, Guillet, Carole

المصدر: Richter, Clara; Hafner, Jürg; Schuermann, Manuel; Tanadini, Matteo; Trisconi, Nisia; Schmid-Grendelmeier, Peter; Kündig, Thomas; Nägeli, Mirjam; Brüggen, Marie-Charlotte; Guillet, Carole (2023). Dupilumab for Chronic Prurigo: Case Series on Effectiveness, Safety, and Quality of Life. Dermatology, 239(5):811-817.

مصطلحات موضوعية: Dermatology Clinic, 610 Medicine & health, Dermatology

الوصف: Background: Chronic prurigo (CPG) is a pruritic skin disease, characterized by an itch-scratch cycle and scarring. It reduces patients’ quality of life (QoL). Dupilumab is a monoclonal human IgG antibody that inhibits signaling of the interleukin 4 (IL-4) and interleukin 13 (IL-13) pathways through blockade of the IL-4 receptor. Patients with CPG who receive dupilumab often report great improvement in itch and overall QoL. We therefore reviewed our experience in order to follow up on QoL, safety, and treatment response in patients with CPG who received dupilumab. Methods: We conducted a real-world retrospective single-center case series. Outcomes were assessed by phone interviews and photographs using validated questionnaires and scores. Demographic data were obtained from the hospital files. Follow-up was up to 2 years. We assessed QoL with the Dermatology Life Quality Index (DLQI) and the Itchy quality of life questionnaire (ItchyQoL). Numerical Rating Scale (NRS) was used to assess itch. Prurigo lesions were documented with the Prurigo activity and severity score (PAS). Results: Ten patients were included in this study. Results were reported up to 2 years after treatment with dupilumab. The response variables for DLQI, ItchyQoL, NRS, and PAS analyses showed a statistically significant decrease over time (DLQI: p ≤ 0.0001 [−0.84; −1.27], ItchyQoL: p ≤ 0.0001 [−9.89; −18.69], NRS maximum and average: p ≤ 0.0001 [−0.52; −0.86] and p ≤ 0.0001 [−0.55; −0.94], and PAS number of lesions: p = 0.0005 [−1.70; −5.28]). The percent decrease after 1 year of treatment (this estimate is based on model estimates) ranges from −42% to −82%. Four (40%) patients reported mild side effects. No serious side effects were reported. Conclusion: Dupilumab treatment of CGP for up to 2 years is associated with improved QoL and less itching.

وصف الملف: application/pdf

العلاقة: https://www.zora.uzh.ch/id/eprint/240147/1/5._Dupilumab_for_chronic_prurigo_case_series_on_effectiveness__safety__and_quality_of_life.pdfTest; info:pmid/37369187; urn:issn:1018-8665

الإتاحة: https://doi.org/10.5167/uzh-24014710.1159/000531708Test
https://www.zora.uzh.ch/id/eprint/240147Test/
https://www.zora.uzh.ch/id/eprint/240147/1/5._Dupilumab_for_chronic_prurigo_case_series_on_effectiveness__safety__and_quality_of_life.pdfTest

المؤلفون: Brunner, Lorenz, id_orcid:0 000-0001-5959-4948, He, Yuliang, Cousin, Nikola, Scholl, Jeannette, Albin, Livia K., Schmucki, Bianca, Supersaxo, Sandrin, Restivo, Gaetana, Hafner, Jürg, Neri, Dario, id_orcid:0 000-0001-5234-7370, Werner, Sabine, Detmar, Michael

المصدر: Cells, 12 (3)

مصطلحات موضوعية: wound healing, diabetes mellitus, inflammation, lymphangiogenesis, VEGF-C

الوصف: Chronic wounds represent a major therapeutic challenge. Lymphatic vessel function is impaired in chronic ulcers but the role of lymphangiogenesis in wound healing has remained unclear. We found that lymphatic vessels are largely absent from chronic human wounds as evaluated in patient biopsies. Excisional wound healing studies were conducted using transgenic mice with or without an increased number of cutaneous lymphatic vessels, as well as antibody-mediated inhibition of lymphangiogenesis. We found that a lack of lymphatic vessels mediated a proinflammatory wound microenvironment and delayed wound closure, and that the VEGF-C/VEGFR3 signaling axis is required for wound lymphangiogenesis. Treatment of diabetic mice (db/db mice) with the F8–VEGF-C fusion protein that targets the alternatively spliced extra domain A (EDA) of fibronectin, expressed in remodeling tissue, promoted wound healing, and potently induced wound lymphangiogenesis. The treatment also reduced tissue inflammation and exerted beneficial effects on the wound microenvironment, including myofibroblast density and collagen deposition. These findings indicate that activating the lymphatic vasculature might represent a new therapeutic strategy for treating chronic non-healing wounds. ; ISSN:2073-4409

وصف الملف: application/application/pdf

العلاقة: info:eu-repo/semantics/altIdentifier/wos/000929269500001; info:eu-repo/grantAgreement/SNF/Exzellenzbeitrag in Lebenswissenschaften/185392; http://hdl.handle.net/20.500.11850/599074Test

الإتاحة: https://doi.org/20.500.11850/599074Test
https://doi.org/10.3929/ethz-b-000599074Test
https://doi.org/10.3390/cells12030472Test
https://hdl.handle.net/20.500.11850/599074Test

المؤلفون: Esposito, Mauro, Yerly, Laura, Shukla, Prachi, Hermes, Victoria, Sella, Federica, Balazs, Zsolt, Lattmann, Evelyn, Tastanova, Aizhan, Turko, Patrick, Lang, Ramon, Kolm, Isabel, Staeger, Ramon, Kuonen, François, Krauthammer, Michael, Hafner, Juerg, Levesque, Mitchell P, Restivo, Gaetana

المصدر: Br J Dermatol ; ISSN:1365-2133

الوصف: Basal cell carcinoma (BCC) is the most frequently diagnosed skin cancer and the most common malignancy in humans. Different morphological subtypes of BCC are associated with low- or high-risk of recurrence and aggressiveness, but the underlying biology of how the individual subtypes arise remains largely unknown. Because the majority of BCCs appear to arise from mutations in the same pathway, we hypothesized that BCC development, growth and invasive potential is also influenced by the tumor microenvironment and in particular by cancer-associated fibroblasts (CAFs) and their secreted factors.

العلاقة: https://doi.org/10.1093/bjd/ljae258Test; https://pubmed.ncbi.nlm.nih.gov/38916477Test

الإتاحة: https://doi.org/10.1093/bjd/ljae258Test
https://pubmed.ncbi.nlm.nih.gov/38916477Test

المؤلفون: Hiebert, Paul, Martyts, Anastasiya, Schwestermann, Jonas, Janke, Katharina, Hafner, Jürg, Boukamp, Petra, Mazza, Edoardo, Werner, Sabine

المصدر: Hiebert, Paul; Martyts, Anastasiya; Schwestermann, Jonas; Janke, Katharina; Hafner, Jürg; Boukamp, Petra; Mazza, Edoardo; Werner, Sabine (2022). Activation of Nrf2 in fibroblasts promotes a skin aging phenotype via an Nrf2-miRNA-collagen axis. Matrix Biology, 113:39-60.

مصطلحات موضوعية: Dermatology Clinic, 610 Medicine & health, Molecular Biology

الوصف: Aging is associated with progressive skin fragility and a tendency to tear, which can lead to severe clinical complications. The transcription factor NRF2 is a key regulator of the cellular antioxidant response, and pharmacological NRF2 activation is a promising strategy for the prevention of age-related diseases. Using a combination of molecular and cellular biology, histology, imaging and biomechanical studies we show, however, that constitutive genetic activation of Nrf2 in fibroblasts of mice suppresses collagen and elastin expression, resulting in reduced skin strength as seen in aged mice. Mechanistically, the "aging matrisome" results in part from direct Nrf2-mediated overexpression of a network of microRNAs that target mRNAs of major skin collagens and other matrix components. Bioinformatics and functional studies revealed high NRF2 activity in aged human fibroblasts in 3D skin equivalents and human skin biopsies, highlighting the translational relevance of the functional mouse data. Together, these results identify activated NRF2 as a promoter of age-related molecular and biomechanical skin features. Keywords: Aging; Collagen; Extracellular matrix; Nrf2; Skin mechanics; miRNA

وصف الملف: application/pdf

العلاقة: https://www.zora.uzh.ch/id/eprint/224948/1/1_s2.0_S0945053X22001147_main222.pdfTest; info:pmid/36367485; urn:issn:0945-053X

الإتاحة: https://doi.org/10.5167/uzh-22494810.1016/j.matbio.2022.09.002Test
https://www.zora.uzh.ch/id/eprint/224948Test/
https://www.zora.uzh.ch/id/eprint/224948/1/1_s2.0_S0945053X22001147_main222.pdfTest

المؤلفون: Restivo, Gaetana, Tastanova, Aizhan, Balázs, Zsolt, Panebianco, Federica, Diepenbruck, Maren, Ercan, Caner, Preca, Bodgan-T, Hafner, Jürg, Weber, Walter P, Kurzeder, Christian, Vetter, Marcus, Soysal, Simone Münst, Beisel, Christian, Bentires-Alj, Mohamed, Piscuoglio, Salvatore, Krauthammer, Michael, Levesque, Mitchell P

المصدر: Restivo, Gaetana; Tastanova, Aizhan; Balázs, Zsolt; Panebianco, Federica; Diepenbruck, Maren; Ercan, Caner; Preca, Bodgan-T; Hafner, Jürg; Weber, Walter P; Kurzeder, Christian; Vetter, Marcus; Soysal, Simone Münst; Beisel, Christian; Bentires-Alj, Mohamed; Piscuoglio, Salvatore; Krauthammer, Michael; Levesque, Mitchell P (2022). Live slow-frozen human tumor tissues viable for 2D, 3D, ex vivo cultures and single-cell RNAseq. Communications Biology, 5:1144.

مصطلحات موضوعية: Dermatology Clinic, 610 Medicine & health, General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology, Medicine (miscellaneous)

الوصف: Biobanking of surplus human healthy and disease-derived tissues is essential for diagnostics and translational research. An enormous amount of formalin-fixed and paraffin-embedded (FFPE), Tissue-Tek OCT embedded or snap-frozen tissues are preserved in many biobanks worldwide and have been the basis of translational studies. However, their usage is limited to assays that do not require viable cells. The access to intact and viable human material is a prerequisite for translational validation of basic research, for novel therapeutic target discovery, and functional testing. Here we show that surplus tissues from multiple solid human cancers directly slow-frozen after resection can subsequently be used for different types of methods including the establishment of 2D, 3D, and ex vivo cultures as well as single-cell RNA sequencing with similar results when compared to freshly analyzed material.

وصف الملف: application/pdf

العلاقة: https://www.zora.uzh.ch/id/eprint/224947/1/ZORA_s42003_022_04025_0.pdfTest; info:pmid/36307545; urn:issn:2399-3642

الإتاحة: https://doi.org/10.5167/uzh-22494710.1038/s42003-022-04025-0Test
https://www.zora.uzh.ch/id/eprint/224947Test/
https://www.zora.uzh.ch/id/eprint/224947/1/ZORA_s42003_022_04025_0.pdfTest

المؤلفون: Devoogdt, Nele, Partsch, Hugo, Heroes, An-Kathleen, De Vrieze, Tessa, De Groef, An, Geraerts, Inge, Damstra, Robert J, Hafner, Jürg, Keeley, Vaughan, Becker, Anja, Mosti, Giovanni, Brouwer, Els, Thomis, Sarah

المصدر: Devoogdt, Nele; Partsch, Hugo; Heroes, An-Kathleen; De Vrieze, Tessa; De Groef, An; Geraerts, Inge; Damstra, Robert J; Hafner, Jürg; Keeley, Vaughan; Becker, Anja; Mosti, Giovanni; Brouwer, Els; Thomis, Sarah (2022). The ICC Compression Questionnaire: A Comprehensive Tool to Evaluate Compression Materials or Devices Applied in Subjects with Lymphedema or Chronic Venous Disease. Lymphatic Research and Biology, 20(2):191-202.

مصطلحات موضوعية: Dermatology Clinic, 610 Medicine & health, Cardiology and Cardiovascular Medicine, chronic venous disease, compression, lymphedema, questionnaire

الوصف: Background: Compression therapy is an important part of the treatment of patients with lymphedema or chronic venous disease. However, there is no validated questionnaire evaluating the effect of compression and its acceptance by the patient. Therefore, the aims of this study were to construct a questionnaire evaluating the effect of compression and its acceptance by the patient, that is, the Dutch ICC Compression Questionnaire (ICC-CQ), to investigate its reliability and validity, and to translate it into English. Methods and Results: Eleven experts in applying compression and 51 Dutch patients with experience of using compression were involved in the construction process. One part of the ICC-CQ has to be completed by the patient and evaluates seven domains. The other part has to be completed by the health care provider and comprises three domains. Reliability and validity of the final version was investigated in a new group of 79 Dutch-speaking patients with lymphedema or chronic venous disease, wearing compression garments (N = 52) or bandages (N = 27). Except for one domain, the Intraclass Correlation Coefficients for test-rest/interrater reliability ranged from 0.55 to 0.93. Cronbach's alpha for internal consistency ranged from 0.71 to 0.97. Eighty-nine percent of the patients fully understood the questionnaire indicating good face validity, and 87% found it complete indicating good content validity. Construct validity was considered good since 10 out of 11 hypotheses were accepted. Conclusion: The ICC-CQ is the first reliable and valid questionnaire evaluating different kinds of compression and the experience by patients with lymphedema or chronic venous disease.

وصف الملف: application/pdf

العلاقة: https://www.zora.uzh.ch/id/eprint/219855/1/lrb.2020.0125.pdfTest; info:pmid/33781091; urn:issn:1539-6851

الإتاحة: https://doi.org/10.5167/uzh-21985510.1089/lrb.2020.0125Test
https://www.zora.uzh.ch/id/eprint/219855Test/
https://www.zora.uzh.ch/id/eprint/219855/1/lrb.2020.0125.pdfTest

المؤلفون: Urosevic-Maiwald, Mirjana, Hardenberg, Jan-Hendrik B, Hafner, Jürg, Brüggen, Marie-Charlotte

المصدر: Urosevic-Maiwald, Mirjana; Hardenberg, Jan-Hendrik B; Hafner, Jürg; Brüggen, Marie-Charlotte (2022). Cocaine/Levamisole-Induced, Skin-Limited ANCA-Associated Vasculitis with Pyoderma Gangrenosum-like Presentation. Dermatopathology, 9(3):207-211.

مصطلحات موضوعية: Dermatology Clinic, 610 Medicine & health, General Engineering

الوصف: The use of levamisole as the most frequent adulterant of cocaine has merged in previously unknown toxicities, notably a disease entity called cocaine/levamisole-associated autoimmune syndrome (CLAAS). Clinically, CLAAS can manifest with diverse cutaneous and extracutaneous features sharing common laboratory findings (neutropenia, autoantibody patterns). We report the case of a cocaine-abusing female patient with relapsing episodes of painful ulcers, worsening and expanding over a three-year period. The case exhibited all features of a drug-induced, skin-limited, ANCA-associated vasculitis, evolving over time to PG-like findings. In both disease stages, the patient responded well to the cessation of cocaine exposure and systemic glucocorticosteroids. This case demonstrates the continuous nature of cutaneous CLAAS manifestations in a single patient. CLAAS has become a major public health issue in the at-risk group of cocaine users, and clinicians should be alert of this condition when treating cocaine users presenting with single or multiple skin ulcerations.

وصف الملف: application/pdf

العلاقة: https://www.zora.uzh.ch/id/eprint/219858/1/dermatopathology_09_00026_v2.pdfTest; info:pmid/35892479; urn:issn:2296-3529

الإتاحة: https://doi.org/10.5167/uzh-21985810.3390/dermatopathology9030026Test
https://www.zora.uzh.ch/id/eprint/219858Test/
https://www.zora.uzh.ch/id/eprint/219858/1/dermatopathology_09_00026_v2.pdfTest

المؤلفون: Koulouri, Angeliki, Buset, Caroline, Hafner, Jürg, Kuonen, François

المصدر: Koulouri, Angeliki; Buset, Caroline; Hafner, Jürg; Kuonen, François (2022). Prise en charge des ulcères chroniques: la greffe en pastilles. Revue Médicale Suisse, 18(775):604-607.

مصطلحات موضوعية: Dermatology Clinic, 610 Medicine & health, General Medicine

الوصف: Les ulcères chroniques représentent un problème dermatologique courant et donc une source majeure de dépenses dans les pays occidentaux. La greffe de peau est une intervention chirurgicale au cours de laquelle la peau ou un substitut de peau est transplanté afin de favoriser la cicatrisation d’une plaie. Cet article a pour but de faire le point sur les différentes catégories de greffe, leurs indications dans la prise en charge des ulcères chroniques des membres inférieurs en soulignant la place des greffes en pastilles dans l’arsenal thérapeutique à disposition. Chronic ulcers are a common but important dermatological problem and a major source of expense in the western countries. Skin graft is a surgical procedure in which skin or skin substitute is transplanted in order to close a wound. This article aims to review the different categories of grafts, their indications for the healing of chronic ulcers of the lower limbs, emphasizing the position of punch grafts in the treatment arsenal.

وصف الملف: application/pdf

العلاقة: https://www.zora.uzh.ch/id/eprint/219854/1/RevMed_Greffes.pdfTest; info:pmid/35353456; urn:issn:1660-9379

الإتاحة: https://doi.org/10.5167/uzh-21985410.53738/revmed.2022.18.775.604Test
https://www.zora.uzh.ch/id/eprint/219854Test/
https://www.zora.uzh.ch/id/eprint/219854/1/RevMed_Greffes.pdfTest