Browsing by Subject "SKIN"

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  • Clement, Cristina C.; D'Alessandro, Angelo; Thangaswamy, Sangeetha; Chalmers, Samantha; Furtado, Raquel; Spada, Sheila; Mondanelli, Giada; Ianni, Federica; Gehrke, Sarah; Gargaro, Marco; Manni, Giorgia; Lopez Cara, Luisa Carlota; Runge, Peter; Tsai, Wanxia Li; Karaman, Sinem; Arasa, Jorge; Fernandez-Rodriguez, Ruben; Beck, Amanda; Macchiarulo, Antonio; Gadina, Massimo; Halin, Cornelia; Fallarino, Francesca; Skobe, Mihaela; Veldhoen, Marc; Moretti, Simone; Formenti, Silvia; Demaria, Sandra; Soni, Rajesh K.; Galarini, Roberta; Sardella, Roccaldo; Lauvau, Gregoire; Putterman, Chaim; Alitalo, Kari; Grohmann, Ursula; Santambrogio, Laura (2021)
    Tryptophan catabolism is a major metabolic pathway utilized by several professional and non-professional antigen presenting cells to maintain immunological tolerance. Here we report that 3-hydroxy-l-kynurenamine (3-HKA) is a biogenic amine produced via an alternative pathway of tryptophan metabolism. In vitro, 3-HKA has an anti-inflammatory profile by inhibiting the IFN-gamma mediated STAT1/NF-kappa Beta pathway in both mouse and human dendritic cells (DCs) with a consequent decrease in the release of pro-inflammatory chemokines and cytokines, most notably TNF, IL-6, and IL12p70. 3-HKA has protective effects in an experimental mouse model of psoriasis by decreasing skin thickness, erythema, scaling and fissuring, reducing TNF, IL-1 beta, IFN-gamma, and IL-17 production, and inhibiting generation of effector CD8(+) T cells. Similarly, in a mouse model of nephrotoxic nephritis, besides reducing inflammatory cytokines, 3-HKA improves proteinuria and serum urea nitrogen, overall ameliorating immune-mediated glomerulonephritis and renal dysfunction. Overall, we propose that this biogenic amine is a crucial component of tryptophan-mediated immune tolerance. 3-hydroxy-L-kynurenamine (3-HKA) is a metabolite deriving from a lateral pathway of tryptophan catabolism. Here the authors identify 3-HKA as a biogenic amine and show it has anti-inflammatory properties that can protect mice against psoriasis and nephrotoxic nephritis.
  • Karvonen, V.; Harjama, L.; Heliö, Krista; Kettunen, K.; Elomaa, O.; Koskenvuo, J. W.; Kere, J.; Weckström, S.; Holmström, M.; Saarela, J.; Ranki, A.; Heliö, T.; Hannula-Jouppi, K. (2022)
    Background PPKs represent a heterogeneous group of disorders with hyperkeratosis of palmar and/or plantar skin. PPK, hair shaft abnormalities, cardiomyopathy and arrhythmias can be caused by mutations in desmosomal genes, e.g. desmoplakin (DSP). PPK should trigger genetic testing to reveal mutations with possible related cardiac disease. Objectives To report a large multigenerational family with a novel DSP mutation associated with early-onset PPK and adult-onset cardiomyopathy and arrhythmias. Methods A custom-designed in-house panel of 35 PPK related genes was used to screen mutations in the index patient with focal PPK. The identified DSP mutation was verified by Sanger sequencing. DNA samples from 20 members of the large multigenerational family were sequenced for the DSP mutation. Medical records were reviewed. Clinical dermatological evaluation was performed, including light microscopy of hair samples. Cardiac evaluation included clinical examination, echocardiography, cardiac magnetic resonance imaging (CMR), electrocardiogram (ECG), Holter monitoring and laboratory tests. Results We identified a novel autosomal dominant truncating DSP c.2493delA p.(Glu831Aspfs*33) mutation associated with dilated cardiomyopathy (DCM) with arrhythmia susceptibility and focal PPK as an early cutaneous sign. The mutation was found in nine affected family members, but not in any unaffected members. Onset of dermatological findings preceded cardiac symptoms which were variable and occurred at adult age. Conclusions We report a novel truncating DSP mutation causing focal PPK with varying severity and left ventricular dilatation and ventricular extrasystoles. This finding emphasizes the importance of genetic diagnosis in patients with PPK for clinical counselling and management of cardiomyopathies and arrhythmias.
  • Cuesta-Mateos, Carlo; Fuentes, Patricia; Schrader, Alexandra; Juarez-Sanchez, Raquel; Loscertales, Javier; Mateu-Albero, Tamara; Vega-Piris, Lorena; Espartero-Santos, Marina; Marcos-Jimenez, Ana; Sanchez-Lopez, Blanca Andrea; Perez-Garcia, Yaiza; Jungherz, Dennis; Oberbeck, Sebastian; Wahnschaffe, Linus; Kreutzman, Anna; Andersson, Emma I.; Mustjoki, Satu; Faber, Edgar; Urzainqui, Ana; Fresno, Manuel; Stamatakis, Kostantino; Alfranca, Arantzazu; Terron, Fernando; Herling, Marco; Toribio, Maria Luisa; Munoz-Calleja, Cecilia (2020)
    T-cell prolymphocytic leukemia (T-PLL) is a poor prognostic disease with very limited options of efficient therapies. Most patients are refractory to chemotherapies and despite high response rates after alemtuzumab, virtually all patients relapse. Therefore, there is an unmet medical need for novel therapies in T-PLL. As the chemokine receptor CCR7 is a molecule expressed in a wide range of malignancies and relevant in many tumor processes, the present study addressed the biologic role of this receptor in T-PLL. Furthermore, we elucidated the mechanisms of action mediated by an anti-CCR7 monoclonal antibody (mAb) and evaluated whether its anti-tumor activity would warrant development towards clinical applications in T-PLL. Our results demonstrate that CCR7 is a prognostic biomarker for overall survival in T-PLL patients and a functional receptor involved in the migration, invasion, and survival of leukemic cells. Targeting CCR7 with a mAb inhibited ligand-mediated signaling pathways and induced tumor cell killing in primary samples. In addition, directing antibodies against CCR7 was highly effective in T-cell leukemia xenograft models. Together, these findings make CCR7 an attractive molecule for novel mAb-based therapeutic applications in T-PLL, a disease where recent drug screen efforts and studies addressing new compounds have focused on chemotherapy or small molecules.
  • Riihila, Pilvi; Nissinen, Liisa; Farshchian, Mehdi; Kallajoki, Markku; Kivisaari, Atte; Meri, Seppo; Grenman, Reidar; Peltonen, Sirkku; Peltonen, Juha; Pihlajaniemi, Taina; Heljasvaara, Ritva; Kahari, Veli-Matti (2017)
    Cutaneous squamous cell carcinoma (cSCC) is one of the most common metastatic skin cancers with increasing incidence. We examined the roles of complement component C3 and complement factor B (CFB) in the growth of cSCC. Analysis of cSCC cell lines (n = 8) and normal human epidermal kerati-nocytes (n = 11) with real-time quantitative PCR and Western blotting revealed up-regulation of C3 and CFB expression in cSCC cells. Immunohistochemical staining revealed stronger tumor cell specific Labeling for C3 and CFB in invasive cSCCs (n = 71) and recessive dystrophic epidermolysis bullosa-associated cSCCs (n = 11) than in cSCC in situ (n = 69), actinic keratoses (n = 63), and normal skin (n = 5). Significant up-regulation of C3 and CFB mRNA expression was noted in chemically induced mouse cSCCs, compared to benign papillomas. Knockdown of C3 and CFB expression inhibited migration and proliferation of cSCC cells and resulted in potent inhibition of extracellular signal regulated kinase 1/2 activation. Knockdown of C3 and CFB markedly inhibited growth of human cSCC xenograft tumors in vivo. These results provide evidence for the rotes of C3 and CFB in the development of cSCC and identify them as biomarkers and potential therapeutic targets in this metastatic skin cancer.
  • Rahmati Nezhad, Pegah; Riihilae, Pilvi; Knuutila, Jaakko S.; Viiklepp, Kristina; Peltonen, Sirkku; Kallajoki, Markku; Meri, Seppo; Nissinen, Liisa; Kahari, Veli-Matti (2022)
    Simple Summary The incidence of the most common metastatic skin malignancy, cutaneous squamous cell carcinoma (cSCC), is growing worldwide, and the prognosis of the metastatic disease is poor. Presently, there are no biomarkers or therapeutic targets for high-risk cSCCs. Recent studies have demonstrated the essential role of autocrine complement synthesis in the progression of cSCC. Here, we have evaluated the role of complement Factor D (FD), the rate-limiting enzyme of the alternative complement pathway, in cSCC development. The results identify FD as a novel biomarker and putative therapeutic target for cSCC and propose the small-molecule FD inhibitor Danicopan as a highly specific drug candidate in the therapy of advanced cSCC. It is expected that the discovery of complement-associated molecular markers for cSCC progression would improve diagnosis, classification, prognostication, and targeted therapy of cSCC and its precursors in the future. Cutaneous squamous cell carcinoma (cSCC) is the most prevalent metastatic skin cancer. Previous studies have demonstrated the autocrine role of complement components in cSCC progression. We have investigated factor D (FD), the key enzyme of the alternative complement pathway, in the development of cSCC. RT-qPCR analysis of cSCC cell lines and normal human epidermal keratinocytes (NHEKs) demonstrated significant up-regulation of FD mRNA in cSCC cells compared to NHEKs. Western blot analysis also showed more abundant FD production by cSCC cell lines. Significantly higher FD mRNA levels were noted in cSCC tumors than in normal skin. Strong tumor cell-associated FD immunolabeling was detected in the invasive margin of human cSCC xenografts. More intense tumor cell-specific immunostaining for FD was seen in the tumor edge in primary and metastatic cSCCs, in metastases, and in recessive dystrophic epidermolysis bullosa-associated cSCCs, compared with cSCC in situ, actinic keratosis and normal skin. FD production by cSCC cells was dependent on p38 mitogen-activated protein kinase activity, and it was induced by interferon-gamma and interleukin-1 beta. Blocking FD activity by Danicopan inhibited activation of extracellular signal-regulated kinase 1/2 and attenuated proliferation of cSCC cells. These results identify FD as a novel putative biomarker and therapeutic target for cSCC progression.
  • Ruokolainen, Lasse; Parkkola, Anna; Karkman, Antti; Sinkko, Hanna; Peet, Aleksandr; Hämäläinen, Anu-Maaria; von Hertzen, Leena; Tillmann, Vallo; Koski, Katriina; Virtanen, Suvi M.; Niemelä, Onni; Haahtela, Tari; Knip, Mikael (2020)
    Background Allergic diseases are more common in Finland than in Estonia, which-according to the biodiversity hypothesis-could relate to differences in early microbial exposures. Methods We aimed at defining possible microbial perturbations preceding early atopic sensitization. Stool, nasal and skin samples of 6-month-old DIABIMMUNE study participants with HLA susceptibility to type 1 diabetes were collected. We compared microbiotas of sensitized (determined by specific IgE results at 18 months of age) and unsensitized Estonian and Finnish children. Results Sensitization was differentially targeted between populations, as egg-specific and birch pollen-specific IgE was more common in Finland. Microbial diversity and community composition also differed; the genusAcinetobacterwas more abundant in Estonian skin and nasal samples. Particularly, the strain-level profile ofAcinetobacter lwoffiiwas more diverse in Estonian samples. Early microbiota was not generally associated with later sensitization. Microbial composition tended to differ between children with or without IgE-related sensitization, but only in Finland. While land-use pattern (ie green areas vs. urban landscapes around the children's homes) was not associated with microbiota as a whole, it associated with the composition of the genusAcinetobacter. Breastfeeding affected gut microbial composition and seemed to protect from sensitization. Conclusions In accordance with the biodiversity hypothesis, our results support disparate early exposure to environmental microbes between Finnish and Estonian children and suggest a significant role of the genusAcinetobacterin the allergy gap between the two populations. The significance of the observed differences for later allergic sensitization remains open.
  • Kluger, Nicolas (2016)
    Tattooing can result in a wide variety of complications, whose prevalence and incidence remain still unclear. Hypersensitivity reactions (or allergies) to tattoo pigments are currently the most common complication on a tattoo, however they are not predictable. Infections are nowadays directly related to the lack of asepsis and hygiene during the tattooing procedure or during the healing phase. Patients with a known cutaneous disease should be warned of a potential risk of localization of their disease to the tattoo. A skin eruption restricted to a tattoo may reveal sarcoidosis. Patients with chronic conditions and/or impaired immunity should discuss with their physician about the possibility and when to have a tattoo.
  • Lagus, Heli; Klaas, Mariliis; Juteau, Susanna; Elomaa, Outi; Kere, Juha; Vuola, Jyrki; Jaks, Viljar; Kankuri, Esko (2019)
    Because molecular memories of past inflammatory events can persist in epidermal cells, we evaluated the long-term epidermal protein expression landscapes after dermal regeneration and in psoriatic inflammation. We first characterized the effects of two dermal regeneration strategies on transplants of indicator split-thickness skin grafts (STSGs) in ten adult patients with deep burns covering more than 20% of their body surface area. After fascial excision, three adjacent areas within the wound were randomized to receive a permanent dermal matrix, a temporary granulation-tissue-inducing dressing or no dermal component as control. Control areas were covered with STSG immediately, and treated areas after two-weeks of dermis formation. Epidermis-dermis-targeted proteomics of one-year-follow-up samples were performed for protein expression profiling. Epidermal expression of axonemal dynein heavy chain 10 (DNAH10) was increased 20-fold in samples having had regenerating dermis vs control. Given the dermal inflammatory component found in our dermal regeneration samples as well as in early psoriatic lesions, we hypothesized that DNAH10 protein expression also would be affected in psoriatic skin samples. We discovered increased DNAH10 expression in inflammatory lesions when compared to unaffected skin. Our results associate DNAH10 expression with cell proliferation and inflammation as well as with the epidermal memory resulting from the previous regenerative signals of dermis. This study (ISRCTN14499986) was funded by the Finnish Ministry of Defense and by government subsidies for medical research.
  • Heliö, Krista; Kangas-Kontio, Tiia; Weckström, Sini; Vanninen, Sari U. M.; Aalto-Setälä, Katriina; Alastalo, Tero-Pekka; Myllykangas, Samuel; Heliö, Tiina M.; Koskenvuo, Juha W. (2020)
    Background Dilated cardiomyopathy (DCM) is a condition characterized by dilatation and systolic dysfunction of the left ventricle in the absence of severe coronary artery disease or abnormal loading conditions. Mutations in the titin (TTN) and lamin A/C (LMNA) genes are the two most significant contributors in familial DCM. Previously mutations in the desmoplakin (DSP) gene have been associated with arrhythmogenic right ventricular cardiomyopathy (ARVC) and more recently with DCM. Methods We describe the cardiac phenotype related to a DSP mutation which was identified in ten unrelated Finnish index patients using next-generation sequencing. Sanger sequencing was used to verify the presence of this DSP variant in the probands' relatives. Medical records were obtained, and clinical evaluation was performed. Results We identified DSP c.6310delA, p.(Thr2104Glnfs*12) variant in 17 individuals of which 11 (65%) fulfilled the DCM diagnostic criteria. This pathogenic variant presented with left ventricular dilatation, dysfunction and major ventricular arrhythmias. Two patients showed late gadolinium enhancement (LGE) and myocardial edema on cardiac magnetic resonance imaging (MRI) that may suggest inflammatory process at myocardium. Conclusions The patients diagnosed with DCM showed an arrhythmogenic phenotype as well as SCD at young age supporting the recently proposed concept of arrhythmogenic cardiomyopathy. This study also demonstrates relatively low penetrance of truncating DSP variant in the probands' family members by the age of 40. Further studies are needed to elucidate the possible relations between myocardial inflammation and pathogenic DSP variants.
  • Karppinen, Toni; Ylianttila, Lasse; Kautiainen, Hannu; Reunala, Timo; Snellman, Erna (2015)
    Empowering heliotherapy aims at clinical healing and improved coping with psoriasis and atopic dermatitis, but evidence of long-term effects is scarce. We studied the effect of 2-week empowering heliotherapy in the Canary Islands on clinical outcome and quality of life in 22 psoriasis and 13 atopic dermatitis patients. Empowerment consisted of meeting peers, sharing experiences and performing physical and mental practices. Using the self-administered PASI (SAPASI) psoriasis was alleviated statistically significantly during heliotherapy (p <0.001), and the treatment effect was still detectable 3 months later (p <0.001). Atopic dermatitis was improved (p <0.001) when assessed with the patient-oriented SCORAD (PO-SCORAD), and the effect was still obvious 3 months later (p = 0.002). During heliotherapy the dermatology life quality index (DLQI) improved in both groups (p <0.001), persisting in atopic patients for up to 3 months (p = 0.002), but not in psoriasis patients. In conclusion, a 2-week empowered heliotherapy showed a long-lasting improvement in psoriasis and atopic dermatitis disease activity, and also in the quality of life of atopic patients.
  • Karppinen, Toni; Laine, Juha-Pekka; Kautiainen, Hannu; Pasternack, Rafael; Reunala, Timo; Snellman, Erna (2017)
  • Miroshnikova, Yekaterina A; Cohen, Idan; Ezhkova, Elena; Wickström, Sara A (2019)
    The skin epidermis is a constantly renewing stratified epithelium that provides essential protective barrier functions throughout life. Epidermal stratification is governed by a step-wise differentiation program that requires precise spatiotemporal control of gene expression. How epidermal self-renewal and differentiation are regulated remains a fundamental open question. Cell-intrinsic and cell-extrinsic mechanisms that modify chromatin structure and interactions have been identified as key regulators of epidermal differentiation and stratification. Here, we will review the recent advances in our understanding of how chromatin modifiers, tissue-specific transcription factors, and force-induced nuclear remodeling processes function to shape chromatin and to control epidermal tissue development and homeostasis.
  • Schmid, Daphne A.; Domingues, Marisa P.; Nanu, Alina; Kluger, Nicolas; de Salvo, Raffaella; Trapp, Sonja (2022)
    Background and Aims Tattoo prevalence has significantly increased over the last decades. Proper tattoo aftercare, such as cleansing, moisturizing, and protection against sunlight, is essential to prevent complications and to keep the beauty of the tattoo. The tolerability, performance, and cosmetic acceptability of two dexpanthenol-containing dermo-cosmetic products, a wash and a sun-care, were investigated on tattooed skin in two separate trials. Methods Two single-center, exploratory, open-label cosmetic studies were conducted between August and November 2020 to evaluate the dexpanthenol-containing dermo-cosmetic products. In the first study, healthy adults applied the 2.5% dexpanthenol-containing wash right after their tattoo session daily for 14 consecutive days. In the second study, healthy adults applied the 2.5% dexpanthenol-containing sun-care sun protection factor 50+ cream on existing tattoos that were daily exposed to sunlight for 28 consecutive days. Clinical examination by a dermatologist and self-assessment through subject questionnaires were used to assess the tolerability, acceptance, ease of use, and cosmetic outcomes of both products. Additionally, transepidermal water loss and moisturization assessments were performed to evaluate skin hydration after use of the sun-care product. Results Both study products were well tolerated, and no product related adverse events were reported during the studies. At least 90% of the study participants appreciated the performance of the dexpanthenol-containing wash and sun-care product, including moisturizing properties, relief of unpleasant sensations, and preservation of the cosmetic appearance of the tattoo. For the sun-care, it was shown that its application supported maintaining the skin barrier of tattooed skin, while keeping it hydrated. Conclusion The 2.5% dexpanthenol-containing wash and sun-care products are well tolerated and appreciated by tattooed subjects. Hence, they represent valid options for tattoo aftercare in line with current recommendations and practice.
  • Jheon, Andrew H.; Li, Chun-Ying; Wen, Timothy; Michon, Frederic; Klein, Ophir D. (2011)
  • Minh Binh Nguyen; Cohen, Idan; Kumar, Vinod; Xu, Zijian; Bar, Carmit; Dauber-Decker, Katherine L.; Tsai, Pai-Chi; Marangoni, Pauline; Klein, Ophir D.; Hsu, Ya-Chieh; Chen, Ting; Mikkola, Marja L.; Ezhkova, Elena (2018)
    Merkel cells are innervated mechanosensory cells responsible for light-touch sensations. In murine dorsal skin, Merkel cells are located in touch domes and found in the epidermis around primary hairs. While it has been shown that Merkel cells are skin epithelial cells, the progenitor cell population that gives rise to these cells is unknown. Here, we show that during embryogenesis, SOX9-positive (+) cells inside hair follicles, which were previously known to give rise to hair follicle stem cells (HFSCs) and cells of the hair follicle lineage, can also give rise to Merkel Cells. Interestingly, while SOX9 is critical for HFSC specification, it is dispensable for Merkel cell formation. Conversely, FGFR2 is required for Merkel cell formation but is dispensable for HFSCs. Together, our studies uncover SOX9(+) cells as precursors of Merkel cells and show the requirement for FGFR2-mediated epithelial signalling in Merkel cell specification.
  • Kim, Christine S.; Ding, Xiaolei; Allmeroth, Kira; Biggs, Leah C.; Kolenc, Olivia I.; L'Hoest, Nina; Chacon-Martinez, Carlos Andres; Edlich-Muth, Christian; Giavalisco, Patrick; Quinn, Kyle P.; Denzel, Martin S.; Eming, Sabine A.; Wickström, Sara A. (2020)
    Stem cells reside in specialized niches that are critical for their function. Upon activation, hair follicle stem cells (HFSCs) exit their niche to generate the outer root sheath (ORS), but a subset of ORS progeny returns to the niche to resume an SC state. Mechanisms of this fate reversibility are unclear. We show that the ability of ORS cells to return to the SC state requires suppression of a metabolic switch from glycolysis to oxidative phosphorylation and glutamine metabolism that occurs during early HFSC lineage progression. HFSC fate reversibility and glutamine metabolism are regulated by the mammalian target of rapamycin complex 2 (mTORC2)-Akt signaling axis within the niche. Deletion of mTORC2 results in a failure to re-establish the HFSC niche, defective hair follicle regeneration, and compromised long-term maintenance of HFSCs. These findings highlight the importance of spatiotemporal control of SC metabolic states in organ homeostasis.
  • Salmivuori, M.; Grönroos, M.; Tani, T.; Pölönen, I.; Räsänen, J.; Annala, L.; Snellman, E.; Neittaanmäki, N. (2020)
    Abstract Background In the photodynamic therapy (PDT) of non-aggressive basal cell carcinomas (BCCs), 5-aminolevulinic acid nanoemulsion (BF-200ALA) has shown non-inferior efficacy when compared with methyl aminolevulinate (MAL), a widely used photosensitizer. Hexyl aminolevulinate (HAL) is an interesting alternative photosensitizer. To our knowledge, this is the first study using HAL-PDT in the treatment of BCCs. Objectives To compare the histological clearance, tolerability (pain and post-treatment reaction), and cosmetic outcome of MAL, BF-200 ALA, and low-concentration HAL in the PDT of non-aggressive BCCs. Methods Ninety-eight histologically verified non-aggressive BCCs met the inclusion criteria, and 54 patients with 95 lesions completed the study. The lesions were randomized to receive LED-PDT in two repeated treatments with MAL, BF-200 ALA, or HAL. Efficacy was assessed both clinically and confirmed histologically at three months by blinded observers. Furthermore, cosmetic outcome, pain, post-treatment reactions fluorescence, and photobleaching were evaluated. Results According to intention-to-treat analyses, the histologically confirmed lesion clearance was 93.8% (95% confidence interval [CI] = 79.9?98.3) for MAL, 90.9% (95% CI = 76.4?96.9) for BF-200 ALA, and 87.9% (95% CI = 72.7?95.2) for HAL, with no differences between the arms (p=0.84). There were no differences between the arms as regards pain, post-treatment reactions, or cosmetic outcome. Conclusions PDT with low-concentration HAL and BF-200 ALA have a similar efficacy, tolerability, and cosmetic outcome compared to MAL. HAL is an interesting new option in dermatological PDT, since good efficacy is achieved with a low concentration.
  • Harjunen, Ville Johannes; Sjö, Petja; Ahmed, Imtiaj; Saarinen, Aino; Farmer, Harry; Salminen, Mikko; Järvelä, Simo; Ruonala, Antti; Jacucci, Giulio; Ravaja, Niklas (2022)
    The tendency to simulate the pain of others within our own sensorimotor systems is a vital component of empathy. However, this sensorimotor resonance is modulated by a multitude of social factors including similarity in bodily appearance, e.g. skin colour. The current study investigated whether increasing self–other similarity via virtual transfer to another colour body reduced ingroup bias in sensorimotor resonance. A sample of 58 white participants was momentarily transferred to either a black or a white body using virtual reality technology. We then employed electroencephalography to examine event-related desynchronization (ERD) in the sensorimotor beta (13–23 Hz) oscillations while they viewed black, white and violet photorealistic virtual agents being touched with a noxious or soft object. While the noxious treatment of a violet agent did not increase beta ERD, amplified beta ERD in response to black agent’s noxious vs soft treatment was found in perceivers transferred to a black body. Transfer to the white body dismissed the effect. Further exploratory analysis implied that the pain-related beta ERD occurred only when the agent and the participant were of the same colour. The results suggest that even short-lasting changes in bodily resemblance can modulate sensorimotor resonance to others’ perceived pain.
  • Lagus, Heli; Kankuri, Esko; Nuutila, Kristo; Juteau, Susanna; Sarlomo-Rikala, Maarit; Vuola, Jyrki (2018)
    Cellular grafts used for skin repair require rapid integration with the host tissue to remain viable and especially to nourish the epidermal cells. Here, we evaluated the responses in the split-thickness skin grafts (STSGs) grafted on three differently treated wound beds: directly on excised wound bed (EX), on an artificial dermal template (DT) and on granulation tissue (GT) induced by cellulose sponge. In ten burn patients, after excision, a test area was divided into three sections: One transplanted with STSG instantaneously and two sections had a pre-treatment for 2 weeks with either DT or a cellulose sponge inducing granulation tissue formation and thereafter grafted with STSGs. One week after grafting, the STSGs on GT demonstrated most endothelial CD31(+) staining, largest average vessel diameters as well as most CD163(+) staining of M2-like macrophages and most MIB1(+) proliferating epidermal cells, suggesting an active regenerative environment. STSGs on DT had smallest vessel diameters and the least CD163(+) macrophages. STSGs on EX had the least CD31(+) cells and the least MIB1(+) proliferating cells. After 3 months, this reactivity in STSGs had subsided, except increased dermal cell proliferation was observed in STSGs on EX. Results show that pre-treatment of wound bed and induction of granulation tissue formation can accelerate host-graft interaction by stimulating graft vasculature and inducing cell proliferation.
  • Peuhu, Emilia; Salomaa, Siiri I.; De Franceschi, Nicola; Potter, Christopher S.; Sundberg, John P.; Pouwels, Jeroen (2017)
    SHARPIN (Shank-Associated RH Domain-Interacting Protein) is a component of the linear ubiquitin chain assembly complex (LUBAC), which enhances TNF-induced NF-kappa B activity. SHARPIN-deficient (Sharpin(cpdm/cpdm)) mice display multi-organ inflammation and chronic proliferative dermatitis (cpdm) due to TNF-induced keratinocyte apoptosis. In cells, SHARPIN also inhibits integrins independently of LUBAC, but it has remained enigmatic whether elevated integrin activity levels in the dermis of Sharpin(cpdm/cpdm) mice is due to increased integrin activity or is secondary to inflammation. In addition, the functional contribution of increased integrin activation to the Sharpin(cpdm/cpdm) phenotype has not been investigated. Here, we find increased integrin activity in keratinocytes from Tnfr1(-/-) Sharpin(cpdm/cpdm) double knockout mice, which do not display chronic inflammation or proliferative dermatitis, thus suggesting that SHARPIN indeed acts as an integrin inhibitor in vivo. In addition, we present evidence for a functional contribution of integrin activity to the Sharpin(cpdm/cpdm) skin phenotype. Treatment with an integrin beta 1 function blocking antibody reduced epidermal hyperproliferation and epidermal thickness in Sharpin(cpdm/cpdm) mice. Our data indicate that, while TNF-induced cell death triggers the chronic inflammation and proliferative dermatitis, absence of SHARPIN-dependent integrin inhibition exacerbates the epidermal hyperproliferation in Sharpin(cpdm/cpdm) mice.