Landscape dynamic network biomarker analysis reveals the tipping point of transcriptome reprogramming to prevent skin photodamage

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.

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Dynamic network biomarker indicates pulmonary metastasis at the tipping point of hepatocellular carcinoma

Nature Communications ◽

10.1038/s41467-018-03024-2 ◽

2018 ◽

Vol 9 (1) ◽

Cited By ~ 47

Author(s):

Biwei Yang ◽

Meiyi Li ◽

Wenqing Tang ◽

Weixin Liu ◽

Si Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Pulmonary Metastasis ◽

Dynamic Network ◽

Tipping Point ◽

Network Biomarker

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Understanding migraine using dynamic network biomarkers

Cephalalgia ◽

10.1177/0333102414550108 ◽

2014 ◽

Vol 35 (7) ◽

pp. 627-630 ◽

Cited By ~ 22

Author(s):

Markus A Dahlem ◽

Jürgen Kurths ◽

Michel D Ferrari ◽

Kazuyuki Aihara ◽

Marten Scheffer ◽

...

Keyword(s):

Mathematical Modeling ◽

Mathematical Models ◽

Dynamic Network ◽

Tipping Point ◽

Trigger Factors ◽

Clinical Neuroscience ◽

Complex Interactions ◽

Network Biomarker ◽

Network Biomarkers ◽

Premonitory Symptoms

Background Mathematical modeling approaches are becoming ever more established in clinical neuroscience. They provide insight that is key to understanding complex interactions of network phenomena, in general, and interactions within the migraine-generator network, in particular. Purpose In this study, two recent modeling studies on migraine are set in the context of premonitory symptoms that are easy to confuse for trigger factors. This causality confusion is explained, if migraine attacks are initiated by a transition caused by a tipping point. Conclusion We need to characterize the involved neuronal and autonomic subnetworks and their connections during all parts of the migraine cycle if we are ever to understand migraine. We predict that mathematical models have the potential to dismantle large and correlated fluctuations in such subnetworks as a dynamic network biomarker of migraine.

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Personalized Early-Warning Signals during Progression of Human Coronary Atherosclerosis by Landscape Dynamic Network Biomarker

Genes ◽

10.3390/genes11060676 ◽

2020 ◽

Vol 11 (6) ◽

pp. 676

Author(s):

Jing Ge ◽

Chenxi Song ◽

Chengming Zhang ◽

Xiaoping Liu ◽

Jingzhou Chen ◽

...

Keyword(s):

Early Warning ◽

Coronary Atherosclerosis ◽

Dynamic Network ◽

Tipping Point ◽

Warning Signals ◽

Metabolomics Data ◽

Early Warning Signals ◽

Network Biomarkers ◽

Landscape Dynamic ◽

Major Factors

Coronary atherosclerosis is one of the major factors causing cardiovascular diseases. However, identifying the tipping point (predisease state of disease) and detecting early-warning signals of human coronary atherosclerosis for individual patients are still great challenges. The landscape dynamic network biomarkers (l-DNB) methodology is based on the theory of dynamic network biomarkers (DNBs), and can use only one-sample omics data to identify the tipping point of complex diseases, such as coronary atherosclerosis. Based on the l-DNB methodology, by using the metabolomics data of plasma of patients with coronary atherosclerosis at different stages, we accurately detected the early-warning signals of each patient. Moreover, we also discovered a group of dynamic network biomarkers (DNBs) which play key roles in driving the progression of the disease. Our study provides a new insight into the individualized early diagnosis of coronary atherosclerosis and may contribute to the development of personalized medicine.

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Basic Red 51, a permitted semi-permanent hair dye, is cytotoxic to human skin cells: Studies in monolayer and 3D skin model using human keratinocytes (HaCaT)

Toxicology Letters ◽

10.1016/j.toxlet.2014.03.007 ◽

2014 ◽

Vol 227 (2) ◽

pp. 139-149 ◽

Cited By ~ 22

Author(s):

Thalita B. Zanoni ◽

Manoela Tiago ◽

Fernanda Faião-Flores ◽

Silvia B. de Moraes Barros ◽

Aalt Bast ◽

...

Keyword(s):

Human Skin ◽

Human Keratinocytes ◽

Skin Model ◽

Hair Dye ◽

Skin Cells ◽

Human Skin Cells ◽

3D Skin

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Generation of a plant polypeptide library and screening with a 3D skin model

Biochemical Society Transactions ◽

10.1042/bst029a111 ◽

2001 ◽

Vol 29 (5) ◽

pp. A111-A111

Author(s):

I. Horan ◽

A.M. O'Brien ◽

P.T. Tomkins

Keyword(s):

Skin Model ◽

3D Skin

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Mixture toxicity of methylisothiazolinone and propylene glycol on the skin irritation tested by human 3D skin model, EpiDerm™

Toxicology Letters ◽

10.1016/j.toxlet.2016.06.1696 ◽

2016 ◽

Vol 258 ◽

pp. S189-S190

Author(s):

K. Park ◽

J. Park ◽

H. Lee ◽

J. Lee

Keyword(s):

Propylene Glycol ◽

Skin Irritation ◽

Mixture Toxicity ◽

Skin Model ◽

3D Skin

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Determination of tipping point in course of PM2.5 organic extracts-induced malignant transformation by dynamic network biomarkers

Journal of Hazardous Materials ◽

10.1016/j.jhazmat.2021.128089 ◽

2021 ◽

pp. 128089

Author(s):

Shen Chen ◽

Daochuan Li ◽

Dianke Yu ◽

Miao Li ◽

Lizhu Ye ◽

...

Keyword(s):

Malignant Transformation ◽

Dynamic Network ◽

Tipping Point ◽

Organic Extracts ◽

Network Biomarkers

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Nrf2 Overexpression for the Protective Effect of Skin-Derived Precursors against UV-Induced Damage: Evidence from a Three-Dimensional Skin Model

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/7021428 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 3

Author(s):

Dehai Xian ◽

Xia Xiong ◽

Jixiang Xu ◽

Li Xian ◽

Qirong Lei ◽

...

Keyword(s):

Three Dimensional ◽

Cell Swelling ◽

Histological Structure ◽

Related Factor ◽

Type I ◽

Apoptotic Cells ◽

Ros Scavenging ◽

Skin Model ◽

Protective Genes ◽

3D Skin

Background. Skin photodamage is associated with ultraviolet- (UV-) induced reactive oxygen species (ROS) overproduction and nuclear factor erythroid 2-related factor 2 (Nrf2) inactivation. In our previous study, skin-derived precursors (SKPs) were shown to ameliorate a UV-induced damage in mice, probably through Nrf2 activation and ROS scavenging. Objective. To clarify the mechanism underlying the photoprotective effect of SKPs against UV-induced damage in a three-dimensional (3D) skin model. Methods. The Nrf2 gene in SKPs was modified using lentiviral infection, and 3D skin models were reconstructed with keratinocytes and fibroblasts on the basis of type I collagen. Subsequently, these models were divided into the following six groups: normal, model, overexpressed, control, silenced, and negative control groups. Prior to irradiation, respective SKPs were injected into the last four groups. Next, all groups except the normal group were exposed to UVA+UVB. Lastly, the pathological and molecular-biological techniques were employed to determine the parameters. Additionally, LY294002, a PI3K inhibitor, was used to investigate the roles of PI3K/Akt and Nrf2/hemeoxygenase-1 (HO-1) in SKP photoprotection. Results. Normal 3D skin models appeared as milky-white analogs with a clear, well-arranged histological structure. After the skin was exposed to irradiation, it exhibited cell swelling and a disorganized structure and developed nuclear condensation with numerous apoptotic cells. The expressions of cellular protective genes and Nrf2/HO-1/PI3K/Akt proteins remarkably decreased, which were accompanied by increased oxidative stress and decreased antioxidants (P<0.05). However, these phenomena were reversed by nrf2-overexpressing SKPs. The 3D skin in the overexpressed group showed mild swelling, neatly arranged cells, and few apoptotic cells. Cellular protective genes and Nrf2/HO-1/PI3K/Akt proteins were highly expressed, and the oxidative biomarkers were remarkably ameliorated (P<0.05). Nevertheless, the expression of these proteins decreased after LY294002 pretreatment regardless of SKP treatment or not. Meanwhile, there were increases in both UV-induced apoptotic cells and ROS level accompanied with SOD and GPX decrease in the presence of LY294002. Conclusions. Evidence from the 3D skin model demonstrates that the protection of SKPs against UV-mediated damage is primarily via the PI3K/Akt-mediated activation of the Nrf2/HO-1 pathway, indicating that SKPs may be a promising candidate for the treatment of photodermatoses.

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