1.
Identification of Casiopeina II-gly secondary targets through a systems pharmacology approach.
de Anda-Jáuregui, G, Espinal-Enríquez, J, Hur, J, Alcalá-Corona, SA, Ruiz-Azuara, L, Hernández-Lemus, E
Computational biology and chemistry. 2019;:127-132
Abstract
Casiopeinas are a group of copper-based compounds designed to be used as less toxic, more efficient chemotherapeutic agents. In this study, we analyzed the in vitro effects of Casiopeina II-gly on the expression of canonical biological pathways. Using microarray data from HeLa cell lines treated with Casiopeina II-gly, we identified biological pathways that are perturbed after treatment. We present a novel approach integrating pathway analysis and network theory: The Pathway Crosstalk Network. We constructed a network with deregulated pathways, featuring links between those pathways that crosstalk with each other. We identified modules grouping deregulated pathways that are functionally related. Through this approach, we were able to identify three features of Casiopeina treatment: (a) Perturbation of signaling pathways, related to induction of apoptosis; (b) perturbation of metabolic pathways, and (c) activation of immune responses. These findings can be useful to drive new experimental exploration on their role in adverse effects and efficacy of Casiopeinas.
2.
Dandruff/seborrhoeic dermatitis is characterized by an inflammatory genomic signature and possible immune dysfunction: transcriptional analysis of the condition and treatment effects of zinc pyrithione.
Mills, KJ, Hu, P, Henry, J, Tamura, M, Tiesman, JP, Xu, J
The British journal of dermatology. 2012;:33-40
Abstract
BACKGROUND Dandruff/seborrhoeic dermatitis is a common scalp condition that is characterized by flakes, pruritus and sometimes mild erythema. These symptoms reflect tissue level events that are poorly understood at the molecular level. OBJECTIVES The purpose of this work was: (i) to compare gene expression profiles in subjects with dandruff vs. those of subjects without dandruff to determine the key physiological disruptions manifest in the condition; and (ii) to determine the effect on this profile of treatment with a shampoo containing potentiated zinc pyrithione (ZPT). METHODS In study 1, scalp biopsies were taken from 16 normal subjects and from involved and uninvolved sites in 15 subjects with dandruff. In study 2, 30 subjects with dandruff were treated for 3 weeks with a commercial ZPT shampoo (n = 15) or a vehicle (n = 15), and scalp lesional biopsies were collected at baseline and end of study for transcriptomic analysis. RNA was extracted from all biopsies and Affymetrix gene chips were used to analyse transcriptomic profiles, followed by bioinformatic analysis. RESULTS Analysis of study 1 biopsies revealed more than 7000 individual probes differentially regulated in dandruff lesional skin relative to normal. Enriched Gene Ontology categories included: lipid metabolism, immune response, response to stimulus, apoptosis, cell proliferation, and epidermal development. The most striking feature of lesional skin relative to normal was the reciprocal expression of induced inflammatory genes and repressed lipid metabolism genes. Induced inflammatory genes were also enriched in dandruff uninvolved skin, suggesting the existence of predisposing factors associated with inflammation. Many genes increased in lesional skin were increased at the level of protein in stratum corneum samples (e.g. IL-1RA, S100A8, S100A9, S100A11, IL-8). Under conditions known to improve overall scalp condition, the ZPT shampoo treatment in study 2 produced a transcriptomic profile resembling that of normal scalp skin. CONCLUSIONS These data provide novel insights into the nature of dandruff and the therapeutic action of potentiated ZPT-containing shampoo, and provide a basis to explore many new mechanistic questions related to these topics.
3.
Antimonial therapy induces circulating proinflammatory cytokines in patients with cutaneous leishmaniasis.
Kocyigit, A, Gur, S, Gurel, MS, Bulut, V, Ulukanligil, M
Infection and immunity. 2002;(12):6589-91
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Abstract
The objective of this study was to evaluate the association between antimonial therapy and circulating levels of proinflammatory cytokines in patients with cutaneous leishmaniasis (CL). Patients were treated with conventional chemotherapy by using pentavalent antimonium salts (Glucantime) for 3 weeks. Circulating plasma levels of the proinflammatory cytokines interleukin-1beta (IL-1beta), IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha) were determined for CL patients and healthy subjects before and 3 weeks after the treatment was started. Plasma IL-1beta, IL-6, IL-8, and TNF-alpha levels were significantly higher for pretreatment CL patients than for healthy subjects. Proinflammatory cytokines significantly increased after 21 days postinfection compared to levels for the pretreatment patients. These increments were approximately 3-fold for IL-1beta and TNF-alpha levels, 10-fold for IL-6 levels, and 20-fold for IL-8 levels in patients with CL. Taken together these results indicate that circulating proinflammatory cytokine levels were increased in patients with CL as a consequence of host defense strategies, and antimonial therapy may induce these cytokines by affecting the macrophage or other components of the host defense system.