3d skin
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2022 ◽  
Vol 11 (1) ◽  
Author(s):  
Sarah Fink ◽  
Anke Burmester ◽  
Uta‐Christina Hipler ◽  
Claudia Neumeister ◽  
Marcus R. Götz ◽  
...  

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 88
Author(s):  
Natalia Karolina Kordulewska ◽  
Justyna Topa ◽  
Robert Stryiński ◽  
Beata Jarmołowska

The Toll-like receptor (TLR) family signature has been linked to the etiopathology of atopic dermatitis (AD), a chronic inflammatory skin disease associated with skin barrier dysfunction and immune system imbalance. We aimed to investigate whether osthole (a plant-derived compound) can inhibit the genetic profile of key genes associated with TLR2 signaling (TIRAP, MyD88, IRAK1, TRAF6, IκBα, NFκB) after stimulation with LPS or histamine in a 3D in vitro model of AD. Overexpression of the aforementioned genes may directly increase the secretion of proinflammatory cytokines (CKs) and chemokines (ChKs), which may exacerbate the symptoms of AD. Relative gene expressions were quantified by qPCR and secretion of CKs and ChKs was evaluated by ELISA assay. LPS and histamine increased the relative expression of genes related to the TLR2 pathway, and osthole successfully reduced it. In summary, our results show that osthole inhibits the expression of genes associated with the TLR signaling pathway in a skin model of AD. Moreover, the secretion of CKs and ChKs after treatment of AD with osthole in a 3D skin model in vitro suggests the potential of osthole as a novel compound for the treatment of AD.


2021 ◽  
Vol 23 (1) ◽  
pp. 299
Author(s):  
Nilakshi Barua ◽  
Lin Huang ◽  
Carmen Li ◽  
Ying Yang ◽  
Mingjing Luo ◽  
...  

The invasion of skin tissue by Staphylococcus aureus is mediated by mechanisms that involve sequential breaching of the different stratified layers of the epidermis. Induction of cell death in keratinocytes is a measure of virulence and plays a crucial role in the infection progression. We established a 3D-organotypic keratinocyte-fibroblast co-culture model to evaluate whether a 3D-skin model is more effective in elucidating the differences in the induction of cell death by Methicillin-resistant Staphylococcus aureus (MRSA) than in comparison to 2D-HaCaT monolayers. We investigated the difference in adhesion, internalization, and the apoptotic index in HaCaT monolayers and our 3D-skin model using six strains of MRSA representing different clonal types, namely, ST8, ST30, ST59, ST22, ST45 and ST239. All the six strains exhibited internalization in HaCaT cells. Due to cell detachment, the invasion study was limited up to two and a half hours. TUNEL assay showed no significant difference in the cell death induced by the six MRSA strains in the HaCaT cells. Our 3D-skin model provided a better insight into the interactions between the MRSA strains and the human skin during the infection establishment as we could study the infection of MRSA in our skin model up to 48 h. Immunohistochemical staining together with TUNEL assay in the 3D-skin model showed co-localization of the bacteria with the apoptotic cells demonstrating the induction of apoptosis by the bacteria and revealed the variation in bacterial transmigration among the MRSA strains. The strain representing ST59 showed maximum internalization in HaCaT cells and the maximum cell death as measured by Apoptotic index in the 3D-skin model. Our results show that 3D-skin model might be more likely to imitate the physiological response of skin to MRSA infection than 2D-HaCaT monolayer keratinocyte cultures and will enhance our understanding of the difference in pathogenesis among different MRSA strains.


Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 35
Author(s):  
Nilakshi Barua ◽  
Ying Yang ◽  
Lin Huang ◽  
Margaret Ip

The vancomycin-resistance associated sensor/regulator, VraSR two-component regulatory-system (VraSR), regulates virulence and the response of Staphylococcus aureus (SA) to environmental stress. To investigate the role of VraSR in SA skin and soft tissue infections (SSTI), we inactivated the VraSR of a clinical CA-MRSA ST30 strain by insertional mutation in vraR gene using the TargeTron-Gene Knockout System. We constructed an organotypic keratinocyte fibroblast co-culture (3D-skin model) and a humanized mouse as SSTI infection models. In the 3D-skin model, inactivation of VraSR in the strains ST30 and USA300 showed 1-log reduction in adhesion and internalization (p < 0.001) compared to the respective wildtype. The mutant strains of ST30 (p < 0.05) and USA300-LAC (p < 0.001) also exhibited reduced apoptosis. The wildtype ST30 infection in the humanized mouse model demonstrated increased skin lesion size and bacterial burden compared to BALB/c mice (p < 0.01). The response of the humanized mouse towards the MRSA infection exhibited human similarity indicating that the humanized mouse SSTI model is more suitable for evaluating the role of virulence determinants. Inactivation of VraSR in ST30 strain resulted in decreased skin lesion size in the humanized mouse SSTI model (p < 0.05) and reduction in apoptotic index (p < 0.01) when compared with the wildtype. Our results reveal that inactivating the VraSR system may be a potent anti-virulence approach to control MRSA infection.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Deyuan Zou ◽  
Tian Chen ◽  
Wenjing He ◽  
Jiacheng Bao ◽  
Ching Hua Lee ◽  
...  

AbstractRobust boundary states epitomize how deep physics can give rise to concrete experimental signatures with technological promise. Of late, much attention has focused on two distinct mechanisms for boundary robustness—topological protection, as well as the non-Hermitian skin effect. In this work, we report the experimental realizations of hybrid higher-order skin-topological effect, in which the skin effect selectively acts only on the topological boundary modes, not the bulk modes. Our experiments, which are performed on specially designed non-reciprocal 2D and 3D topolectrical circuit lattices, showcases how non-reciprocal pumping and topological localization dynamically interplays to form various states like 2D skin-topological, 3D skin-topological-topological hybrid states, as well as 2D and 3D higher-order non-Hermitian skin states. Realized through our highly versatile and scalable circuit platform, theses states have no Hermitian nor lower-dimensional analog, and pave the way for applications in topological switching and sensing through the simultaneous non-trivial interplay of skin and topological boundary localizations.


Author(s):  
Chengming Zhang ◽  
Hong Zhang ◽  
Jing Ge ◽  
Tingyan Mi ◽  
Xiao Cui ◽  
...  

Abstract Skin, as the outmost layer of human body, is frequently exposed to environmental stressors including pollutants and ultraviolet (UV), which could lead to skin disorders. Generally, skin response process to ultraviolet B (UVB) irradiation is a nonlinear dynamic process, with unknown underlying molecular mechanism of critical transition. Here, the landscape dynamic network biomarker (l-DNB) analysis of time series transcriptome data on 3D skin model was conducted to reveal the complicated process of skin response to UV irradiation at both molecular and network levels. The advanced l-DNB analysis approach showed that: (i) there was a tipping point before critical transition state during pigmentation process, validated by 3D skin model; (ii) 13 core DNB genes were identified to detect the tipping point as a network biomarker, supported by computational assessment; (iii) core DNB genes such as COL7A1 and CTNNB1 can effectively predict skin lightening, validated by independent human skin data. Overall, this study provides new insights for skin response to repetitive UVB irradiation, including dynamic pathway pattern, bi-phasic response, and DNBs for skin lightening change, and enables us to further understand the skin resilience process after external stress.


2021 ◽  
Vol 141 (10) ◽  
pp. S167
Author(s):  
S. Cadau ◽  
M. Gault ◽  
N. Berthelemy ◽  
D. Gauché ◽  
C. Pons ◽  
...  
Keyword(s):  

mBio ◽  
2021 ◽  
Author(s):  
Lisa Lemoine ◽  
Dilan Bayrambey ◽  
Alexander Roloff ◽  
Christoph Hutzler ◽  
Andreas Luch ◽  
...  

Exposure to xenobiotics has repeatedly been associated with adverse health effects. While the majority of reported cases relate to direct substance effects, there is increasing evidence that microbiome-dependent metabolism of xenobiotic substances likewise has direct adverse effects on the host.


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