scholarly journals OTULIN inhibits RIPK1-mediated keratinocyte necroptosis to prevent skin inflammation in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hannah Schünke ◽  
Ulrike Göbel ◽  
Ivan Dikic ◽  
Manolis Pasparakis
Keyword(s):  
Skin Lesion ◽  
Kinase Activity ◽  
Skin Inflammation ◽  
Skin Lesions ◽  
Autoinflammatory Syndrome ◽  
Toll Like Receptor ◽  
Lesion Development ◽  
Ubiquitin Chain ◽  
Multiple Organs ◽  
Activity Dependent

AbstractLinear ubiquitination regulates inflammatory and cell death signalling. Deficiency of the linear ubiquitin chain-specific deubiquitinase, OTULIN, causes OTULIN-related autoinflammatory syndrome (ORAS), a systemic inflammatory pathology affecting multiple organs including the skin. Here we show that mice with epidermis-specific OTULIN deficiency (OTULINE-KO) develop inflammatory skin lesions that are driven by TNFR1 signalling in keratinocytes and require RIPK1 kinase activity. OTULINE-KO mice lacking RIPK3 or MLKL have only very mild skin inflammation, implicating necroptosis as an important etiological mediator. Moreover, combined loss of RIPK3 and FADD fully prevents skin lesion development, showing that apoptosis also contributes to skin inflammation in a redundant function with necroptosis. Finally, MyD88 deficiency suppresses skin lesion development in OTULINE-KO mice, suggesting that toll-like receptor and/or IL-1 signalling are involved in mediating skin inflammation. Thus, OTULIN maintains homeostasis and prevents inflammation in the skin by inhibiting TNFR1-mediated, RIPK1 kinase activity-dependent keratinocyte death and primarily necroptosis.

scholarly journals FAC-Net: Feedback Attention Network Based on Context Encoder Network for Skin Lesion Segmentation

Sensors ◽  
2021 ◽  
Vol 21 (15) ◽  
pp. 5172
Author(s):  
Yuying Dong ◽  
Liejun Wang ◽  
Shuli Cheng ◽  
Yongming Li
Keyword(s):  
Skin Lesion ◽  
Real Life ◽  
Good Deal ◽  
Experimental Tests ◽  
Skin Lesions ◽  
Lesion Segmentation ◽  
Attention Network ◽  
Effective Feedback ◽  
Public Datasets ◽  
Learning Architectures

Considerable research and surveys indicate that skin lesions are an early symptom of skin cancer. Segmentation of skin lesions is still a hot research topic. Dermatological datasets in skin lesion segmentation tasks generated a large number of parameters when data augmented, limiting the application of smart assisted medicine in real life. Hence, this paper proposes an effective feedback attention network (FAC-Net). The network is equipped with the feedback fusion block (FFB) and the attention mechanism block (AMB), through the combination of these two modules, we can obtain richer and more specific feature mapping without data enhancement. Numerous experimental tests were given by us on public datasets (ISIC2018, ISBI2017, ISBI2016), and a good deal of metrics like the Jaccard index (JA) and Dice coefficient (DC) were used to evaluate the results of segmentation. On the ISIC2018 dataset, we obtained results for DC equal to 91.19% and JA equal to 83.99%, compared with the based network. The results of these two main metrics were improved by more than 1%. In addition, the metrics were also improved in the other two datasets. It can be demonstrated through experiments that without any enhancements of the datasets, our lightweight model can achieve better segmentation performance than most deep learning architectures.

scholarly journals ASCU-Net: Attention Gate, Spatial and Channel Attention U-Net for Skin Lesion Segmentation

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 501
Author(s):  
Xiaozhong Tong ◽  
Junyu Wei ◽  
Bei Sun ◽  
Shaojing Su ◽  
Zhen Zuo ◽  
...  
Keyword(s):  
Skin Lesion ◽  
Contextual Information ◽  
Skin Lesions ◽  
Medical Image Segmentation ◽  
Learning Networks ◽  
Wide Range ◽  
Accurate Performance ◽  
Relevant Field ◽  
Skin Smooth ◽  
Smooth Transitions

Segmentation of skin lesions is a challenging task because of the wide range of skin lesion shapes, sizes, colors, and texture types. In the past few years, deep learning networks such as U-Net have been successfully applied to medical image segmentation and exhibited faster and more accurate performance. In this paper, we propose an extended version of U-Net for the segmentation of skin lesions using the concept of the triple attention mechanism. We first selected regions using attention coefficients computed by the attention gate and contextual information. Second, a dual attention decoding module consisting of spatial attention and channel attention was used to capture the spatial correlation between features and improve segmentation performance. The combination of the three attentional mechanisms helped the network to focus on a more relevant field of view of the target. The proposed model was evaluated using three datasets, ISIC-2016, ISIC-2017, and PH2. The experimental results demonstrated the effectiveness of our method with strong robustness to the presence of irregular borders, lesion and skin smooth transitions, noise, and artifacts.

scholarly journals Essential role of IRAK-4 protein and its kinase activity in Toll-like receptor–mediated immune responses but not in TCR signaling

2007 ◽  
Vol 204 (5) ◽  
pp. 1013-1024 ◽  
Author(s):  
Tatsukata Kawagoe ◽  
Shintaro Sato ◽  
Andreas Jung ◽  
Masahiro Yamamoto ◽  
Kosuke Matsui ◽  
...  
Keyword(s):  
Immune Responses ◽  
Kinase Activity ◽  
Interleukin 1 ◽  
Cell Receptor ◽  
Nuclear Factor Κb ◽  
Toll Like Receptor ◽  
Tcr Signaling ◽  
Mitogen Activated Protein

Interleukin-1 receptor–associated kinase 4 (IRAK-4) was reported to be essential for the Toll-like receptor (TLR)– and T cell receptor (TCR)–mediated signaling leading to the activation of nuclear factor κB (NF-κB). However, the importance of kinase activity of IRAK family members is unclear. In this study, we investigated the functional role of IRAK-4 activity in vivo by generating mice carrying a knockin mutation (KK213AA) that abrogates its kinase activity. IRAK-4KN/KN mice were highly resistant to TLR-induced shock response. The cytokine production in response to TLR ligands was severely impaired in IRAK-4KN/KN as well as IRAK-4−/− macrophages. The IRAK-4 activity was essential for the activation of signaling pathways leading to mitogen-activated protein kinases. TLR-induced IRAK-4/IRAK-1–dependent and –independent pathways were involved in early induction of NF-κB–regulated genes in response to TLR ligands such as tumor necrosis factor α and IκBζ. In contrast to a previous paper (Suzuki, N., S. Suzuki, D.G. Millar, M. Unno, H. Hara, T. Calzascia, S. Yamasaki, T. Yokosuka, N.J. Chen, A.R. Elford, et al. 2006. Science. 311:1927–1932), the TCR signaling was not impaired in IRAK-4−/− and IRAK-4KN/KN mice. Thus, the kinase activity of IRAK-4 is essential for the regulation of TLR-mediated innate immune responses.

scholarly journals Prevalence and risk of appearence of skin lesions considered to be cutaneous markers of diabetes in a population group in bihor county

2012 ◽  
Vol 19 (3) ◽  
pp. 285-290
Author(s):  
Denisa Kovacs ◽  
Luiza Demian ◽  
Aurel Babeş
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Skin Lesion ◽  
Skin Diseases ◽  
Population Group ◽  
Skin Lesions ◽  
Diabetic Patients ◽  
Cutaneous Lesions

Abstract Objectives: The aim of the study was to calculate the prevalence rates and risk ofappearance of cutaneous lesions in diabetic patients with both type-1 and type-2diabetes. Material and Method: 384 patients were analysed, of which 47 had type-1diabetes (T1DM), 140 had type-2 diabetes (T2DM) and 197 were non-diabeticcontrols. Results: The prevalence of the skin lesions considered markers of diabeteswas 57.75% in diabetics, in comparison to 8.12% in non-diabetics (p<0.01). The riskof skin lesion appearance is over 7 times higher in diabetic patients than in nondiabetics.In type-1 diabetes the prevalence of skin lesions was significantly higherthan in type-2 diabetes, and the risk of skin lesion appearance is almost 1.5 timeshigher in type-1 diabetes than type-2 diabetes compared to non-diabetic controls.Conclusions: The diabetic patients are more susceptible than non-diabetics todevelop specific skin diseases. Patients with type-1 diabetes are more affected.

AI-Enabled Support System for Melanoma Detection and Classification

2021 ◽  
Vol 10 (4) ◽  
pp. 58-75
Author(s):  
Vivek Sen Saxena ◽  
Prashant Johri ◽  
Avneesh Kumar
Keyword(s):  
Artificial Intelligence ◽  
Machine Learning ◽  
Skin Lesion ◽  
Performance Metrics ◽  
Similarity Index ◽  
Skin Lesions ◽  
Machine Learning Algorithms ◽  
Lesion Area ◽  
Melanoma Detection ◽  
Grabcut Algorithm

Skin lesion melanoma is the deadliest type of cancer. Artificial intelligence provides the power to classify skin lesions as melanoma and non-melanoma. The proposed system for melanoma detection and classification involves four steps: pre-processing, resizing all the images, removing noise and hair from dermoscopic images; image segmentation, identifying the lesion area; feature extraction, extracting features from segmented lesion and classification; and categorizing lesion as malignant (melanoma) and benign (non-melanoma). Modified GrabCut algorithm is employed to generate skin lesion. Segmented lesions are classified using machine learning algorithms such as SVM, k-NN, ANN, and logistic regression and evaluated on performance metrics like accuracy, sensitivity, and specificity. Results are compared with existing systems and achieved higher similarity index and accuracy.

scholarly journals SELECTED APPLICATIONS OF DEEP NEURAL NETWORKS IN SKIN LESION DIAGNOSTIC

2021 ◽  
Vol 11 (4) ◽  
pp. 18-21
Author(s):  
Magdalena Michalska
Keyword(s):  
Neural Networks ◽  
Malignant Melanoma ◽  
Skin Lesion ◽  
Deep Neural Networks ◽  
Skin Lesions ◽  
Multiclass Classification ◽  
Features Selection ◽  
Lesion Segmentation ◽  
Dermatological Diseases ◽  
Segmentation Process

The article provides an overview of selected applications of deep neural networks in the diagnosis of skin lesions from human dermatoscopic images, including many dermatological diseases, including very dangerous malignant melanoma. The lesion segmentation process, features selection and classification was described. Application examples of binary and multiclass classification are given. The described algorithms have been widely used in the diagnosis of skin lesions. The effectiveness, specificity, and accuracy of classifiers were compared and analysed based on available datasets.

scholarly journals SPOROTRIKOSIS LIMFOKUTAN DIAGNOSIS HISTOPATOLOGI DAN SITOLOGI

2013 ◽  
Vol 2 (1) ◽  
Author(s):  
Poppy M. Lintong ◽  
Inneke V. Sumolang
Keyword(s):  
Skin Lesion ◽  
Fine Needle Aspiration ◽  
Fine Needle Aspiration Biopsy ◽  
Histopathological Examination ◽  
Sporothrix Schenckii ◽  
Giant Cells ◽  
Skin Lesions ◽  
Needle Aspiration ◽  
Fine Needle ◽  
Left Hand

Abstract: Diagnosis of sporotrichosis associated with lymphocutaneous nodules was made based on the histopathological examination of skin lesions and the cytology of fine needle aspiration biopsy (FNAB). A case of sporotrichosis in a 63-year-old man was reported with papules and nodules spread along the back of the left hand, forearm, and arm. The histopatho-logical examination showed infiltration of PMNs, granulomas, and giant cells in the dermis and epidermis, along with hyperplasia and microabscesses. Sporothrix schenckii was not found in the skin lesion tissues. However, in the FNAB cytology examination of lymphocutaneus nodules we found spores of Sporothrix schenckii in the cytoplasma of histiocytes besides granuloma and infiltration of PMNs. Key words: sporothrix schenckii, histopathology, FNAB cytology.  Abstrak: Diagnosis sporotrikosis kulit dengan nodul limfokutan ditegakkan melalui pemerik-saan histopatologi pada lesi kulit dan sitologi biopsi aspirasi jarum halus pada nodul limfo-kutan. Kami melaporkan kasus sporotrikosis pada laki-laki berusia 63 tahun dengan papul-papul dan nodul-nodul eritematosa pada dorsum manus, antebrakium, dan brakium sinistra. Pemeriksaan histopatologi jaringan biopsi dari lesi kulit menunjukkan reaksi radang, gambaran granuloma, dan sel datia dalam dermis dan epidermis, dengan mikroabses disertai hiperplasia. Tidak ditemukan jamur Sporothrix schenckii dalam potongan jaringan histopatologi. Hasil pemeriksaan sitologi biopsi aspirasi jarum halus pada nodul limfokutan memperlihatkan adanya spora-spora jamur Sporothrix schenckii dalam sitoplasma sel-sel histiosit disamping  terdapatnya bentuk granuloma dalam infiltrat radang. Kata kunci: sporothrix schenckii, histopatologi, sitologi biopsi aspirasi jarum halus.

scholarly journals ZBP1 induces inflammatory signaling via RIPK3 and promotes SARS-CoV-2-induced cytokine expression

2021 ◽  
Author(s):  
Ruoshi Peng ◽  
Xuan Wang-Kan ◽  
Manja Idorn ◽  
Felix Y Zhou ◽  
Susana L Orozco ◽  
...  
Keyword(s):  
Cell Death ◽  
Signaling Pathway ◽  
Kinase Activity ◽  
Caspase 8 ◽  
Dependent Manner ◽  
Innate Immune Responses ◽  
Inflammatory Signaling ◽  
Antiviral Responses ◽  
Nucleic Acid Sensor ◽  
Activity Dependent

AbstractCOVID-19 caused by the SARS-CoV-2 virus remains a threat to global health. The disease severity is mediated by cell death and inflammation, which regulate both the antiviral and the pathological innate immune responses. ZBP1, an interferon-induced cytosolic nucleic acid sensor, facilitates antiviral responses via RIPK3. Although ZBP1-mediated cell death is widely described, whether and how it promotes inflammatory signaling is unclear. Here, we report a ZBP1-induced inflammatory signaling pathway that depends on ubiquitination and RIPK3’s scaffolding ability independently of cell death. In human cells, ZBP1 associates with RIPK1 and RIPK3 as well as ubiquitin ligases cIAP1 and LUBAC. RIPK1 and ZBP1 are ubiquitinated to promote TAK1- and IKK-mediated inflammatory signaling. Additionally, RIPK1 recruits the p43/41-caspase-8-p43-FLIP heterodimer to suppress RIPK3 kinase activity, which otherwise promotes inflammatory signaling in a kinase activity-dependent manner. Lastly, we show that ZBP1 contributes to SARS-CoV-2-induced cytokine production. Taken together, we describe a ZBP1-RIPK1-RIPK3-mediated inflammatory signaling pathway relayed by the scaffolding role of RIPKs and regulated by caspase-8. Our results suggest the ZBP1 pathway contributes to inflammation in response to SARS-CoV-2 infection.

scholarly journals TGF-beta1 (transforming growth factor-beta1)-mediated adhesion of gastric carcinoma cells involves a decrease in Ras/ERKs (extracellular-signal-regulated kinases) cascade activity dependent on c-Src activity

2004 ◽  
Vol 379 (1) ◽  
pp. 141-150 ◽  
Author(s):  
Hwang-Phill KIM ◽  
Mi-Sook LEE ◽  
Jiyon YU ◽  
Jin-Ah PARK ◽  
Hyun-Soon JONG ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Gastric Carcinoma ◽  
Kinase Activity ◽  
Transforming Growth Factor ◽  
Carcinoma Cells ◽  
Matrix Proteins ◽  
Src Family Kinase ◽  
Extracellular Signal ◽  
Activity Dependent ◽  
Tgf Β1

Signalling by integrin-mediated cell anchorage to extracellular matrix proteins is co-operative with other receptor-mediated signalling pathways to regulate cell adhesion, spreading, proliferation, survival, migration, differentiation and gene expression. It was observed that an anchorage-independent gastric carcinoma cell line (SNU16) became adherent on TGF-β1 (transforming growth factor β1) treatment. To understand how a signal cross-talk between integrin and TGF-β1 pathways forms the basis for TGF-β1 effects, cell adhesion and signalling activities were studied using an adherent subline (SNU16Ad, an adherent variant cell line derived from SNU16) derived from the SNU16 cells. SNU16 and SNU16Ad cells, but not integrin α5-expressing SNU16 cells, showed an increase in adhesion on extracellular matrix proteins after TGF-β1 treatment. This increase was shown to be mediated by an integrin α3 subunit, which was up-regulated in adherent SNU16Ad cells and in TGF-β1-treated SNU16 cells, compared with the parental SNU16 cells. After TGF-β1 treatment of SNU16Ad cells on fibronectin, Tyr-416 phosphorylation of c-Src was increased, but Ras-GTP loading and ERK1/ERK2 (extracellular-signal-regulated kinases 1 and 2) activity were decreased, which showed a dependence on c-Src family kinase activity. Studies on adhesion and signalling activities using pharmacological inhibitors or by transient-transfection approaches showed that inhibition of ERK1/ERK2 activity increased TGF-β1-mediated cell adhesion slightly, but not the basal cell adhesion significantly, and that c-Src family kinase activity and decrease in Ras/ERKs cascade activity were required for the TGF-β1 effects. Altogether, the present study indicates that TGF-β1 treatment causes anchorage-independent gastric carcinoma cells to adhere by an increase in integrin α3 level and a c-Src family kinase activity-dependent decrease in Ras/ERKs cascade activity.

Sign in / Sign up

Export Citation Format

Share Document