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Compared to other wound types, burns may have systemic effects [32, 33], influencing almost all body systems and causing changes in lung, kidney, heart, liver, gastrointestinal tract, bone marrow, and lymphoid organ functioning and multiple organ dysfunction syndrome [32]. At the burn site, inflammatory mediators such as tumor necrosis factor alpha (TNF-α) and interleukins 6, 8, and 1-beta, responsible for systemic effects, are released. Their concentration in serum correlates with the burn surface area. The rise in their concentrations is considered to increase risk of infections, multiple organ dysfunction syndrome, and death [34,35,36].
Mesenchymal stromal cells (MSC) have similar (not identical) features as ESC and can be derived from various tissues, even the skin as mentioned previously [98]. They have a high differentiation potential and a certain degree of plasticity and may generate cells of mesodermal, ectodermal, and endodermal lineages [99]. Moreover, paracrine, trophic, and immunomodulatory MSC properties enable their clinical use [100, 101]. MSC can migrate to the injured tissues, differentiate, and regulate the tissue regeneration by the production of growth factors, cytokines, and chemokines [102]. Their immunomodulatory activity is based on the release of anti-inflammatory cytokines and the inhibition of proliferation of CD4+ and CD8+ natural killer cells, T cells, and B cells. MSC are considered to be hypoimmunogenic because they do not express class I and II molecules of the major histocompatibility complex (MHC) and co-stimulatory proteins (e.g., CD40, CD80, CD86). Therefore, the transplantation of allogenic MSC has a low risk of the immune rejection [103,104,105]. In burn therapy, adipose-derived stromal cells refined from the stromal vascular fraction are widely applied because of their easy access and isolation procedure and inspiring improvement of the healing processes [106,107,108]. They are showed to preserve their therapeutic effects after freezing that ensures their multiple use [109]. It is worth mentioning that even the freshly isolated stromal vascular fraction is showed to be effective in burn therapy [110], but compared to adipose-derived stromal cells, it can release high concentrations of inflammatory mediators [111]. However, the number of randomized controlled preclinical and clinical trials remains insufficient [106].
Growth factor therapy is to administrate pro-epidermal growth factors to promote wound healing. These growth factors are bioactive molecules secreted by the body whose function is to stimulate the growth and propagation of cells involved in skin wound healing and inflammation. The use of extra-growth factor increases the number of wound-healing cells, causing faster wound healing. Despite their variety, there are five types commonly used as invigorating molecules in wound healing and regaining via benign tissue repair processes (Table 3). They include compounds influencing epidermal tissue regrowth (epidermal growth factor (EGF); hepatocyte growth factor (HGF)), anti-scarring (transforming growth factor (TGF-ß3)), pro-angiogenesis (vascular endothelial growth factor (VEFG); platelet-derived growth factor (PDGF)), and stromal cell growth (fibroblast growth factor (FGF)). A combination of multiple growth factors may efficiently improve cellular functions: proliferation, migration, differentiation, collagen remodeling, inhibition of fibroblast overgrowth, ECM deposition, etc. Therefore, strategies to control growth factors release may prompt skin tissue regeneration. To optimize substance delivery and loading, bioactivity, therapeutic functionality, dosage form stability, etc., it is vital to develop platforms such as hydrogels, microbeads, or tissue-engineered constructs.
Angiogenesis in a defect site can be promoted by PDGF and VEGF. PDGF-BB is approved by FDA for diabetic ulcer treatment [143], but it has low success in clinics probably due to its damage by proteolytic enzymes or low expression of PDGF-receptors. VEGF showed high efficacy in experiments in vivo (e.g., [144]) and passed a phase I trial proving its safety and efficacy in treatment of chronic wounds [145]. To promote vessel formation, both PDGF and VEGF require constant application during a treatment period that has induced research to develop delivery systems with sustained release. For instance, Tan et al. [146] revealed VEGF-loaded collagen scaffolds significantly improved the wound healing processes in diabetic rats followed by the increase in VEGF level in tissue and induced angiogenesis. Moreover, Gorkun et al. [147] showed that VEGF-induced spheroids from adipose-derived stromal cells encapsulated within modified fibrin gel can form tubule-like network that might be interesting as a new approach to enhance angiogenesis in a wound and improve skin tissue regeneration.
In some cases, the use of a single growth factor may be insufficient because of the complexity of molecular pathways and wound chronicity that reveals a need to develop multiple growth factor systems with sustained release. For example, Lai et al. [137] designed a collagen-HA membrane with immobilized VEGF, PDGF, bFGF, and EGF and showed that it efficiently induced the increase in wound healing rate by enhancing collagen deposition and neovasculogenesis compared to the control group.
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While not the worst of Bullock's performances, this 1993 flick comes in last because her character, Diane, is missing for most of it. After being kidnapped from a gas station, her boyfriend, played by Kiefer Sutherland, searches for her for three years. Trust us, the cat-and-mouse game between Sutherland and Diane's abductor isn't worth it. Instead, track down the 1988 Dutch original, Spoorloos, from which this remake is based, and turn on the subtitles for a real scare.
In conventional tracing studies, viruses or dyes are injected into the fat to be retrogradely transported back to the DRG somas and assessed by histology. This indirect measurement is susceptible to varying tracer efficiency across hosts, potentially contributing to the discrepancy observed across animal species6,7,8. Ideally, direct visualization of the entire projection from DRG soma to the target organs, for example, through an axon-filling fluorophore, would provide the most reliable anatomical proof. However, the peripheral branch of the mouse DRG travels several centimetres before reaching its targets, making it impossible to visualize using conventional histology. We recently developed HYBRiD, specifically designed for en bloc fluorescence visualization of large tissues17, paving the way to directly characterize the intact sensory innervation from DRGs to fat.
Lin, Q. Y., Jin, L. J., Cao, Z. H., Lu, Y. N., Xue, H. Y., and Xu, Y. P. Acanthopanax senticosus suppresses reactive oxygen species production by mouse peritoneal macrophages in vitro and in vivo. Phytother.Res 2008;22(6):740-745. View abstract.
Umeyama, A., Shoji, N., Takei, M., Endo, K., and Arihara, S. Ciwujianosides D1 and C1: powerful inhibitors of histamine release induced by anti-immunoglobulin E from rat peritoneal mast cells. J Pharm.Sci. 1992;81(7):661-662. View abstract.
Yim, S, Jeong JuCheol, and Jeong JiHoon. Effect of an extract of Acanthopanax senticosus on restoration of hair loss in mouse. Chung-Ang Journal of Medicine Seoul: Institute of Medical Science, Chung-Ang University College of Medicine 2007;32(4):81-84.
Eschbach LF, Webster MJ, Boyd JC, et al. The effect of siberian ginseng (Eleutherococcus senticosus) on substrate utilization and performance. Int J Sport Nutr Exerc Metab 2000;10:444-51. View abstract.
The gut microbiome has been shown to impact the health of its host, in particular by mediating the impact of diet on host body weight [1,2,3]. Specific interactions between dietary components, the microbiome, and the host are however still cumbersome to determine and confirm. While it is possible to perform such studies in humans, the costs involved, time constraints, and the need to control many confounders make it desirable to conduct such research in other species, where the findings might be predictive of human results. The traditional lab mouse has been widely used for this purpose, but its value has been questioned [4, 5]. Recently, pigs, although much more expensive, have been proposed as an alternative model as they may be closer to humans in phenotype and diet [6, 7]. Pigs have long been known to possess a gastrointestinal tract similar to that of humans and have been used as model animals in nutrition studies [8].
Dog gut microbiome gene catalog in comparison to human, mouse and pig. a Overview of gene catalog generation pipeline. b Phylogenetic relationship of the four hosts considered in this study, obtained by whole genome alignments, as reported by Murphy et al. [10]. c Distribution by phylum of the genes in the dog, human, mouse, and pig gut gene catalogs. d Principal coordinate analysis of genus-level taxonomic distribution in four mammal hosts (including two human cohorts), based on abundance-weighted Jaccard distance. e Mapping rates of reads from each of the four hosts when recruited against the human gene catalog. f Overlap of gene catalogs at 95% identity between the catalogs of the four species considered (in thousands of genes). g Principal coordinate analysis of SNP-based differentiation of strains from human and dog for the two most abundant species in dogs 350c69d7ab
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