Cutaneous wounds, a type of soft tissue injury, are difficult to heal in aging. Differentiation, migration, proliferation, and apoptosis of skin cells are identified as key factors during wound healing processes. Mesenchymal stem cells have been documented as possible candidates for wound healing treatment because their use could augment the regenerative capacity of many tissues. However, the effects of exosomes derived from adipose-derived stem cell (ADSC-exos) on cutaneous wound healing remain to be carefully elucidated. In this present study, HaCaT cells were exposed to hydrogen peroxide (H2 O 2 ) for the establishment of the skin lesion model. Cell Counting Kit-8 assay, migration assay, and flow cytometry assay were conducted to detect the biological function of ADSC-exos in skin lesion model. Finally, the possible mechanism was further investigated using Western blot assay. The successful construction of the skin lesion model was confirmed by results of the enhanced cell apoptosis of HaCaT cells induced by H 2 O 2 , the increased Bax expression and decreased Bcl-2 expression. CD9 and CD63 expression evidenced the existence of ADSC-exos. The results of functional experiments demonstrated that ADSC-exos could prompt cell proliferation and migration of HaCaT cells, and repress cell apoptosis of HaCaT cells. In addition, the activation of Wnt/β-catenin signaling was confirmed by the enhanced expression of β-catenin at the protein level. Collectively, our findings suggest that ADSC-exos play a positive role in cutaneous wound healing possibly via Wnt/β-catenin signaling. Our study may provide new insights into the therapeutic target for cutaneous wound healing.

Adipose mesenchymal stem cell‐derived exosomes promote cell proliferation, migration, and inhibit cell apoptosis via Wnt/β‐catenin signaling in cutaneous wound healing

Abstract In the past decade, the world has experienced a large increase in the number of novel compounds appearing on the illicit drug market for recreational purposes. Such substances are designed to circumvent governmental regulations; the illegal drug manufacturers take a known psychoactive compound reported in the scientific literature and slightly modify its chemical structure in order to produce analogues that will mimic the pharmacological activity of the original substance. Many of these novel substances are sold via the Internet. Among the various chemical classes, synthetic cannabinoid receptor modulators, commonly referred to as “synthetic cannabinoids” have been at the forefront, as demonstrated by the frequency of drug seizures, numerous severe toxic effects, and fatalities associated with some of these substances. This review presents the chemical structures of relevant synthetic cannabinoids and describes their mechanism of action, pharmacological features, metabolic pathways, and structure-activity relationships. It illustrates the approaches used in forensic testing, both for bulk analysis (drug seizures) and for analytical toxicology (biological matrices) and discusses aspects of regulation surrounding this drug class. This report is intended to provide pertinent information for the purposes of informing scientific, medical, social, and governmental bodies about this ever-evolving recreational drug class and the challenges it poses worldwide.

/pdf/the-ongoing-challenge-of-novel-psychoactive-drugs-of-abuse-n9ix9519mp.pdf

The ongoing challenge of novel psychoactive drugs of abuse. Part I. Synthetic cannabinoids (IUPAC Technical Report)

Impaired wound healing is a significant medical problem. Recently, cell-based therapy focused on stem cells has been developed to overcome the challenges of defective wound healing. In this study, we aimed to evaluate the effectiveness of adipose-derived stem cells (ASCs) in promoting wound healing, using different techniques for administering them. Dorsal full-thickness skin defects ( ) were created in three groups of mice that received intravenous ASCs by intravenous injection, intramuscular injection, and topical application, respectively. Three control groups received saline in the same ways. Wound healing was assessed clinically, wounds were examined histologically, and GFP-labelled ASCs were detected with an IVIS imaging system. The results revealed that ASCs accelerated wound healing independent of their mode of administration. Histological examination showed that the ASCs accelerated reepithelialization, and IVIS analysis indicated that many ASCs were present in the wound area and disappeared after wound healing.

/pdf/the-effect-of-adipose-derived-stem-cells-on-wound-healing-w1inqxjogy.pdf

The Effect of Adipose-Derived Stem Cells on Wound Healing: Comparison of Methods of Application

Objective The development of obesity and its metabolic complications is associated with dys-regulation of various intrinsic mechanisms, which control basic metabolic processes via changes in the expression of numerous regulatory genes. The main goal of this work was to study the association between the expression of insulin-like growth factors (IGF1 and IGF2) and IGF-binding proteins and insulin resistance in obese adolescents for evaluation of possible contribution of these genes in development of insulin resistance. Methods The expression of IGF1, IGF2, and IGFBPs mRNA was measured in blood of obese adolescents with normal insulin sensitivity and insulin resistance in comparison with the normal (control) individuals. Results In the blood of obese adolescents with normal insulin sensitivity the expression of IGFBP4, IGFBP5 and HTRA1 genes was down-regulated, but IGFBP2 and IGFBP7 genes up-regulated as compared to control (normal) group. At the same time, no significant changes in IGF1 and IGF2 gene expressions in this group of obese adolescents were found. Insulin resistance in obese adolescents led to up-regulation of IGF2, IGFBP2, and IGFBP7 gene expressions as well as to down-regulation of the expression of IGF1, IGFBP5 and HTRA1 genes in the blood in comparison with the obese patients, which have normal insulin sensitivity. Furthermore, the level of IGFBP4 gene expression was similar in both groups of obese adolescents. Conclusions Results of this investigation provide evidence that insulin resistance in obese adolescents is associated with gene specific changes in the expression of IGF1, IGF2, IGFBP2, IGFBP5, IGFBP7, and HTRA1 genes and these changes possibly contribute to the development of glucose intolerance and insulin resistance.

/pdf/expression-of-genes-encoding-igf1-igf2-and-igfbps-in-blood-6j52wtrg07.pdf

Expression of genes encoding IGF1, IGF2, and IGFBPs in blood of obese adolescents with insulin resistance

Background When vascular endothelial cells are subjected to external stimuli, paracrine hormones and cytokines act on adjacent cells. The regulation of the biological behaviour of cells is closely related to the maintenance of organ function and the occurrence and development of disease. However, it is unclear whether vascular endothelial cells affect the biological behaviour of cells involved in wound repair through autocrine and paracrine mechanisms and ultimately play a role in wound healing. We aimed to verify the effect of the autocrine and paracrine functions of vascular endothelial cells on wound healing. Materials and methods ELISA was used to detect platelet-derived growth factor, basic fibroblast growth factor, epidermal growth factor, and vascular endothelial growth factor in human umbilical vascular endothelial cell-conditioned medium (HUVEC-CM). Different concentrations of HUVEC-CM were used to treat different stem cells. CCK-8 and scratch assays were used to detect the proliferation and migration ability of each cell. A full-thickness dorsal skin defect model was established in mice, and skin wound healing was observed after the local injection of HUVEC-CM, endothelial cell medium (ECM), or normal saline. H&E staining and immunofluorescence were used to observe the gross morphology of the wound tissue, the epithelial cell migration distance, and the expression of CD3 and CD31. Results HUVEC-CM promotes the proliferation and migration of epidermal stem cells, skin fibroblasts, bone marrow mesenchymal stem cells, and HUVECs themselves. Furthermore, HUVEC-CM can promote angiogenesis in mouse skin wounds and granulation tissue formation and can accelerate wound surface epithelialization and collagen synthesis, thereby promoting wound healing. Conclusion Our results clearly suggest that it is practicable and effective to promote wound healing with cytokines secreted by vascular endothelial cells in a mouse model.

/pdf/autocrine-and-paracrine-effects-of-vascular-endothelial-2t11ljd7pj.pdf

Autocrine and Paracrine Effects of Vascular Endothelial Cells Promote Cutaneous Wound Healing.

OBJECTIVE To study the application value of artificial skin substitute compositely constructed by adipose-derived stem cells and fibrin gel in skin defect. MATERIALS AND METHODS Adipose-derived stem cells (ADSCs) were obtained from healthy pure green fluorescent protein (GFP) transgenic mice and were proved to have multiple differentiation potentials. They compositely constructed artificial skin substitute in vitro with fibrin gel. 24 SD rats of either gender, with the gestational age of 3-5 weeks, were divided into four groups in the experiment, namely model group (autologous skin flap transplantation), adipose-derived stem cell transplantation group, fibrin gel transplantation group and compound transplantation group, 6 rats for each group. At the skin blood flow (measured by applying laser Doppler rheometer) and survival rate of the flap on 7d and 21d respectively, the materials were transplanted at back skin injury (1 cm×1 cm) to prepare tissue slice for routine HE staining. The conditions of wound healing were observed, and the angiogenesis of flap neovascularization was detected by the immunofluorescent assay. RESULTS The skin blood flow, the survival rate of flap and density of neovascularization 7d and 21d after transplantation were significantly higher than those of stem cell group, followed by the model group, with the lowest ones in the fibrin gel group. The differences had statistical significance (p<0.05). The wound healing time of compound group was significantly shorter than that of stem cell group, followed by the model group, with the longest one in the fibrin gel group. The differences had statistical significance (p<0.05). CONCLUSIONS The artificial skin substitute compositely constructed by adipose-derived stem cells and fibrin gel could significantly shorten healing time and improve the survival rate of the flap in skin defect, with better application value.

Experimental study on repairing skin defect by tissue-engineered skin substitute compositely constructed by adipose-derived stem cells and fibrin gel.

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Experimental study on repairing skin defect by tissue-engineered skin substitute compositely constructed by adipose-derived stem cells and fibrin gel.