Anti-Psoriasis Effect of Diclofenac and Celecoxib Using the Tail Model for Psoriasis

Nițescu, Diana Ana-Maria; Păunescu, Horia; Ştefan, Alina Elena; Coman, Laurenţiu; Georgescu, Corneliu Cristian; Stoian, Andrei Constantin; Gologan, Daniela; Fulga, Ion; Coman, Oana Andreia

doi:10.3390/pharmaceutics14040885

Cited by 4 publications

(2 citation statements)

References 28 publications

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“…PGE2 has a multifaceted role in the development of the disease: influencing the differentiation and effector functions of dendritic cells and Th cells (Chizzolini and Brembilla, 2009;, stimulating KCs to secrete chemoattractants, and by dysregulating the normal life cycle of KCs (Tsirvouli et al, 2021). Inhibition of upstream regulators of PGE2 production such as cPLA2a (Ashcroft et al, 2020, 2) and COX-2 (Nițescu et al, 2022) have been described as promising for anti-psoriasis topical treatment, but further clinical studies are needed to assess the potentials of PGE2 signaling as a drug target in psoriasis.…”

Section: Discussionmentioning

confidence: 99%

Patient-specific logical models replicate phenotype responses to psoriatic and anti-psoriatic stimuli

Tsirvouli,

Aker,

Kuiper

2023

Preprint

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Psoriasis is a dermatologic disease that affects 2% of the world population. Psoriasis is characterized by chronic inflammation and aberrant behavior of keratinocytes, which display increased levels of proliferation, and decreased differentiation and apoptosis. Stimulation of keratinocytes by psoriatic cytokines leads to the increased production of immunostimulatory ligands that further attract immune cells and amplify inflammatory responses. Psoriasis can have severe, moderate, or mild outcomes and while these severity levels demand custom medical treatment schemes, assigning an effective treatment to patients with moderate or severe disease is a demanding task. The varied responses of patients to treatments highlight a large disease complexity, demanding that new ways to analyze and integrate patients' molecular profiles are developed to design patient-specific therapies. We have used gene expression values from psoriasis biopsies to separate patients into two clusters, each with distinct expression profiles, but nevertheless not correlating with any of the available clinical data, such as disease severity. When using these gene expression levels in logical model simulations these data became highly descriptive of patient-specific phenotype characteristics. Starting from a psoriatic keratinocyte model that we published recently, we added additional pathways highlighted by a differential gene expression analysis between the subgroups. This included components from the Interleukin-1 family, IFN-alpha/beta and IL-6 signaling pathways. Model personalization was performed by using patient gene expression levels in model configurations, exploiting the PROFILE pipeline. Personalized simulations revealed that the two patient clusters represent more innate immunity-driven, highly inflammatory phenotypes and adaptive immunity-driven, chronic phenotypes, respectively. The model was also able to finely capture differences between responses in patients with a known disease severity. A treatment response analysis among the patient cohort predicted differential responses to the inhibition of psoriatic stimuli, with IL-17, TNFalpha, and PGE2 inhibition reducing proliferation and inflammatory phenotypes. Alternative treatment with PGE2 or TNFalpha inhibition instead of IL-17 was suggested for patients with high NF-kappaB activity and prosurvival factors, such as CREB1. With this project, we aim to highlight the value of combining omics data with logical modeling for the detection of "emergent" phenotypes and for gaining disease knowledge on the individual patient level.

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Section: Discussionmentioning

confidence: 99%

Patient-specific logical models replicate phenotype responses to psoriatic and anti-psoriatic stimuli

Tsirvouli,

Aker,

Kuiper

2023

Preprint

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“…It is used as a dyeing agent in some industries such as leather, textiles, and even hair dyeing. It has also been widely used in histopathology to stain various cells and tissues since the 1800s [ 3 , 4 , 5 ]. HT is composed of two benzene rings and four aromatic hydroxyl groups that do not stain directly.…”

Section: Introductionmentioning

confidence: 99%

Cell Staining Microgels Derived from a Natural Phenolic Dye: Hematoxylin Has Intriguing Biomedical Potential

Sahiner,

Sunol,

Sahiner

2024

Pharmaceutics

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Hematoxylin (HT) as a natural phenolic dye compound is generally used together with eosin (E) dye as H&E in the histological staining of tissues. Here, we report for the first time the polymeric particle preparation from HT as poly(Hematoxylin) ((p(HT)) microgels via microemulsion method in a one-step using a benign crosslinker, glycerol diglycidyl ether (GDE). P(HT) microgels are about 10 µm and spherical in shape with a zeta potential value of −34.6 ± 2.8 mV and an isoelectric point (IEP) of pH 1.79. Interestingly, fluorescence properties of HT molecules were retained upon microgel formation, e.g., the fluorescence emission intensity of p(HT) at 343 nm was about 2.8 times less than that of the HT molecule at λex: 300 nm. P(HT) microgels are hydrolytically degradable and can be controlled by using an amount of crosslinker, GDE, e.g., about 40%, 20%, and 10% of p(HT) microgels was degraded in 15 days in aqueous environments for the microgels prepared at 100, 200, and 300% mole ratios of GDE to HT, respectively. Interestingly, HT molecules at 1000 mg/mL showed 22.7 + 0.4% cell viability whereas the p(HT) microgels exhibited a cell viability of 94.3 + 7.2% against fibroblast cells. Furthermore, even at 2000 mg/mL concentrations of HT and p(HT), the inhibition% of α-glucosidase enzyme were measured as 93.2 ± 0.3 and 81.3 ± 6.3%, respectively at a 0.03 unit/mL enzyme concentration, establishing some potential application of p(HT) microgels for neurogenerative diseases. Moreover, p(HT) microgels showed two times higher MBC values than HT molecules, e.g., 5.0 versus 2.5 mg/mL MIC values against Gram-negative E. coli and Gram-positive S. aureus, respectively.

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Latent space arithmetic on data embeddings from healthy multi-tissue human RNA-seq decodes disease modules

de Weerd,

Guala,

Gustafsson

et al. 2024

Patterns

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Anti-Psoriasis Effect of Diclofenac and Celecoxib Using the Tail Model for Psoriasis

Cited by 4 publications

References 28 publications

Patient-specific logical models replicate phenotype responses to psoriatic and anti-psoriatic stimuli

Patient-specific logical models replicate phenotype responses to psoriatic and anti-psoriatic stimuli

Cell Staining Microgels Derived from a Natural Phenolic Dye: Hematoxylin Has Intriguing Biomedical Potential

Latent space arithmetic on data embeddings from healthy multi-tissue human RNA-seq decodes disease modules

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