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Wound healing approach based on excretory-secretory product and lysate of liver flukes.

ABSTRACT: Exogenous bioactive peptides are considered promising for the wound healing therapy in humans. In this regard, parasitic trematodes proteins may potentially become a new perspective agents. Foodborne trematode Opisthorchis felineus is widespread in Europe and has the ability to stimulate proliferation of bile duct epithelium. In this study, we investigated skin wound healing potential of O. felineus proteins in mouse model. C57Bl/6 mice were inflicted with superficial wounds with 8 mm diameter. Experimental groups included several non-specific controls and specific treatment groups (excretory-secretory product and lysate). After 10 days of the experiment, the percentage of wound healing in the specific treatment groups significantly exceeded the control values. We also found that wound treatment with excretory-secretory product and worm lysate resulted in: (i) inflammation reducing, (ii) vascular response modulating, (iii) type 1 collagen deposition promoting dermal ECM remodeling. An additional proteomic analysis of excretory-secretory product and worm lysate samples was revealed 111 common proteins. The obtained data indicate a high wound-healing potential of liver fluke proteins and open prospects for further research as new therapeutic approaches.

SUBMITTER: Kovner AV

PROVIDER: S-EPMC9751068 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Wound healing approach based on excretory-secretory product and lysate of liver flukes.

Kovner Anna V AV Tarasenko Alena A AA Zaparina Oxana O Tikhonova Olga V OV Pakharukova Maria Y MY Mordvinov Viatcheslav A VA

Scientific reports 20221214 1

Exogenous bioactive peptides are considered promising for the wound healing therapy in humans. In this regard, parasitic trematodes proteins may potentially become a new perspective agents. Foodborne trematode Opisthorchis felineus is widespread in Europe and has the ability to stimulate proliferation of bile duct epithelium. In this study, we investigated skin wound healing potential of O. felineus proteins in mouse model. C57Bl/6 mice were inflicted with superficial wounds with 8 mm diameter. ...[more]

PMID: 36517588

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Project description:AimTo investigate the mechanism of fibroblast cell proliferation stimulated by the Opisthorchis viverrini excretory/secretory (ES) product.MethodsNIH-3T3, mouse fibroblast cells were treated with O. viverrini ES product by non-contact co-cultured with the adult parasites. Total RNA from NIH-3T3 treated and untreated with O. viverrini was extracted, reverse transcribed and hybridized with the mouse 15K complementary DNA (cDNA) array. The result was analyzed by ArrayVision version 5 and GeneSpring version 5 softwares. After normalization, the ratios of gene expression of parasite treated to untreated NIH-3T3 cells of 2-and more-fold upregulated was defined as the differentially expressed genes. The expression levels of the signal transduction genes were validated by semi-quantitative SYBR-based real-time RT-PCR.ResultsAmong a total of 15,000 genes/ESTs, 239 genes with established cell proliferation-related function were 2 fold-and more-up-regulated by O. viverrini ES product compared to those in cells without exposure to the parasitic product. These genes were classified into groups including energy and metabolism, signal transduction, protein synthesis and translation, matrix and structural protein, transcription control, cell cycle and DNA replication. Moreover, the expressions of serine-threonine kinase receptor, receptor tyrosine kinase and collagen production-related genes were up-regulated by O. viverrini ES product. The expression level of signal transduction genes; pkC, pdgfr alpha, jak 1, eps 8, tgf beta 1i4, strap and h ras measured by real-time RT-PCR confirmed their expression levels to those obtained from cDNA array. However, only the up-regulated expression of pkC, eps 8 and tgfbeta 1i4 which are the downstream signaling molecules of either epidermal growth factor (EGF) or transforming growth factor-beta (TGF-beta) showed statistical significance (P < 0.05).ConclusionO. viverrini ES product stimulates the significant changes of gene expression in several functional categories and these mainly include transcripts related to cell proliferation. The TGF-beta and EGF signal transduction pathways are indicated as the possible pathways of O. viverrini-driven cell proliferation.

Project description:The potential of multifunctional wound heal biomaterial relies on the optimal content of therapeutic constituents as well as the desirable physical, chemical, and biological properties to accelerate the healing process. Formulating biomaterials such as amnion or collagen based scaffolds with natural products offer an affordable strategy to develop dressing material with high efficiency in healing wounds. Using image based phenotyping and quantification, we screened natural product derived bioactive compounds for modulators of types I and III collagen production from human foreskin derived fibroblast cells. The identified hit was then formulated with amnion to develop a biomaterial, and its biophysical properties, in vitro and in vivo effects were characterized. In addition, we performed functional profiling analyses by PCR array to understand the effect of individual components of these materials on various genes such as inflammatory mediators including chemokines and cytokines, growth factors, fibroblast stimulating markers for collagen secretion, matrix metalloproteinases, etc., associated with wound healing. FACS based cell cycle analyses were carried out to evaluate the potential of biomaterials for induction of proliferation of fibroblasts. Western blot analyses was done to examine the effect of biomaterial on collagen synthesis by cells and compared to cells grown in the presence of growth factors. This work demonstrated an uncomplicated way of identifying components that synergistically promote healing. Besides, we demonstrated that modulating local wound environment using biomaterials with bioactive compounds could enhance healing. This study finds that the developed biomaterials offer immense scope for healing wounds by means of their skin regenerative features such as anti-inflammatory, fibroblast stimulation for collagen secretion as well as inhibition of enzymes and markers impeding the healing, hydrodynamic properties complemented with other features including non-toxicity, biocompatibility, and safety.

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Wound healing approach based on excretory-secretory product and lysate of liver flukes.

Publications

Wound healing approach based on excretory-secretory product and lysate of liver flukes.

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