Embryonic Porcine Skin Precursors Can Successfully Develop into Integrated Skin without Teratoma Formation Posttransplantation in Nude Mouse Model

How to improve the wound healing quality of severe burn patients is still a challenge due to lack of skin appendages and rete ridges, no matter how much progress has been made in the fields of either stem cell or tissue engineering. We thus systematically studied the growth potential and differentiation capacity of porcine embryonic skin precursors. Implantation of embryonic skin precursors (PESPs) of different gestational ages in nude mice can generate the integrity skin, including epidermis, dermis and skin appendages, such as sweat gland, hair follicle, sebaceous gland, etc.. PESPs of embryonic day 42 possess the maximal growth potential, while, the safe window time of PESPs transplantation for prevention of teratoma risk is E56 or later. In conclusion, PESPs can form the 3 dimensional structures of skin with all necessary skin appendages. Our data strongly indicate that porcine embryonic skin precursors harvested from E56 of minipig may provide new hope for high-quality healing of extensive burns and traumas

Investigating the Role of P311 in the Hypertrophic Scar

The mechanisms of hypertrophic scar formation are not fully understood. We previously screened the differentially expressed genes of human hypertrophic scar tissue and identified P311 gene as upregulated. As the activities of P311 in human fibroblast function are unknown, we examined the distribution of it and the effects of forced expression or silencing of expression of P311. P311 expression was detected in fibroblast-like cells from the hypertrophic scar of burn injury patients but not in peripheral blood mononuclear cells, bone marrow mesenchymal stem cells, epidermal cells or normal skin dermal cells. Transfection of fibroblasts with P311 gene stimulated the expression of alpha-smooth muscle actin (α-SMA), TGF-β1 and α1(I) collagen (COL1A1), and enhanced the contraction of fibroblast populated collagen lattices (FPCL). In contrast, interference of fibroblast P311 gene expression decreased the TGF-β1 mRNA expression and reduced the contraction of fibroblasts in FPCL. These results suggest that P311 may be involved in the pathogenesis of hypertrophic scar via induction of a myofibroblastic phenotype and of functions such as TGF-β1 expression. P311 could be a novel target for the control of hypertrophic scar development

Establishing an Appropriate Pressure for the Transparent Disc Method to Distinguish Early Pressure Injury and Blanchable Erythema

Background: Non-blanchable erythema is used as a diagnostic indicator for stage 1 pressure injury (early PI); it is distinguished from blanchable erythema (BE) by the application of “light pressing”. Considering the low of the accuracy of the degree of pressure applied, it is difficult to use this method in clinical settings. Methods: We constructed models of BE and early PI in order to determine the most appropriate pressure values using the transparent disc method. We observed erythema by using a Dermo-camera to quantify the gray and a* values of the wound area along with a spectrophotometer. Results: BE started to fade at 50 mmHg, while the gray values became statistically significant when the pressure was increased to 100 mmHg (p < 0.05). However, erythema remained even when the pressure was increased to 150 mmHg soon after decompression. By contrast, the early PI was showed to be non-blanchable for the longest time under a pressure of 150 mmHg, but by 18 h it had decreased and the erythema faded more obviously after applying pressure. Conclusions: We proposed that a pressure of 50–100 mmHg was more appropriate for light pressure, but this may vary when different instruments are used. Variations may occur in either BE or early PI, therefore, careful attention should be paid during observations

Treatment of hypertrophic scars with ablative fractional carbon dioxide laser assisted with different topical triamcinolone delivery ways

Objectives: Ablative fractional carbon dioxide laser has been used with triamcinolone to treat hypertrophic scars, resulting in promising success rates. However, there are different topical triamcinolone delivery methods used in scar treatment. To assess the efficacy among the different triamcinolone delivery methods, this study was designed to compare the efficacy and safety of ablative fractional carbon dioxide laser followed by penetration and injection of topical triamcinolone into thicker hypertrophic scars (height score of VSS ≥2). Study design/materials and methods: We performed a retrospective study of 155 thicker hypertrophic scar patients (height score of VSS ≥2), including 88 patients in the triamcinolone external application group and 67 patients in the triamcinolone intralesional injection group. One month after the patients had 3 treatment sessions at 4-week intervals, the scars were assessed by photography, the Vancouver Scar Scale (VSS), durometry and spectrocolorimetry. Any adverse effects were also evaluated. Results: The VSS scores and the hardness of the scars in both groups improved significantly compared to baseline. Moreover, the patients in the triamcinolone intralesional injection group had higher treatment efficacy (19.77 ± 21.25 %) based on their VSS scores than the patients in the triamcinolone external application group (5.94 ± 24.07 %), especially in the improvement of scar pliability, height and hardness. Meanwhile, in the triamcinolone injection group, more patients had mild and moderate improvement than in the triamcinolone application group. However, there were no differences in the distribution of the adverse effects in either group. Conclusions: This study demonstrated that using the ablative fractional carbon dioxide laser followed by different topical triamcinolone delivery methods is effective and safe for thicker hypertrophic scar improvement. The method of using the ablative fractional carbon dioxide laser assisted with triamcinolone injection had a better therapeutic outcome in thicker hypertrophic scars, as compared with triamcinolone penetration

UXT, a novel MDMX-binding protein, promotes glycolysis by mitigating p53-mediated restriction of NF-κB activity

The importance of stress-induced p53 activation has been extensively investigated and well established. How the basal activity of p53 prevents carcinogenesis, however, remains incompletely understood. We report the identification of a novel p53 inhibitor, UXT, which binds to MDMX and suppresses the basal activity of p53. Interestingly, human TCGA database indicates that the UXT gene is frequently amplified in human sarcoma where p53 mutation is rare. We thus used sarcoma as a model to show that UXT acts as an oncogene promoting cell proliferation in vitro and tumor progression in vivo. A screening of 10 major cellular pathways uncovered that UXT-mediated p53 inhibition results in an activation of NF-κB, leading to induction of glycolysis. While elevated glycolytic metabolism provides growth advantage it also renders UXT expressing sarcoma cells heightened sensitivity to glycolysis inhibition. Altogether, our data demonstrate a crucial role for the basal activity of p53 in restriction of NF-κB. By impeding such an activity of p53, UXT unleashes the oncogenic activity of NF-κB resulting in induction of glycolysis fueling carcinogenesis

Effects of pretreated recycled fine aggregates on the mechanical properties and microstructure of alkali-activated mortar

Compared with traditional cement-based binders, alkali-activated binders can be improved upon combination with recycled aggregates to produce a promising and new green construction material. However, during this process, a pretreatment method is needed to alleviate the negative impact of recycled aggregates on the properties of alkali-activated materials. In this study, fly ash (FA), ground granulated blast furnace slag (GGBFS) and recycled powder (RP) were used as precursors, and recycled fine aggregates (RFAs) were used to replace natural fine aggregates (NFAs) to prepare recycled alkali-activated mortar (RAAM). Various RFA replacement ratios (0, 25%, 50% and 100%), pretreatment methods (calcination temperature and carbonation time) and alkaline moduli (0.8, 0.95, 1.1 and 1.25) were investigated. The effects of these parameters on the fresh and hardened properties, chemical composition and microstructure of RAAM were investigated. The results showed that the mechanical properties of RAAM gradually decreased with an increasing RFA replacement ratio due to the poor physical properties of RFA and its poor matrix binding. Two pretreatment methods (optimal calcination at 400 °C and carbonation at 6 h) were effective in improving the properties of RFA and thus the mechanical properties of RAAM. Calcination removed the adhered mortar from RFA and thus improved the mechanical properties of RAAM. Carbonation of RFA enhanced the quality of the attached mortar, which strengthened the RFA and provided better mechanical properties. In addition, microstructural analyses showed that RAAM prepared from pretreated RFA had a dense microstructure and a low critical pore size

A Sponge-Driven Elastic Interface for Lithium Metal Anodes

The lithium (Li) metal is one promising anode for next generation high-energy-density batteries, but the large stress fluctuation and the nonuniform Li deposition upon cycling result in a highly unstable interface of the Li anode. Herein, a simple yet facile engineering of the elastic interface on the Li metal anodes is designed by inserting a melamine sponge between Li and the separator. Driven by the good elasticity of the sponge, the modified Li anode maintains a Coulombic efficiency of 98.8% for 60 cycles and is cyclable at 10 mA cm-2 for 250 cycles, both with a high capacity of 10 mA h cm-2. We demonstrate that the sponge can be used to replace the conventional polypropylene as a porous yet elastic separator, showing superior cycling and rate performance as well. In addition to the efficiency of the elastic interface on the cycling stability, which is further confirmed by an in situ compression-electrochemistry measurement, the porous structure and polar groups of the sponge demonstrate an ability of regulating the transport of Li ions, leading to a uniform deposition of Li and the suppression of Li dendrites in cycling

Spontaneous severe hypercholesterolemia and atherosclerosis lesions in rabbits with deficiency of low-density lipoprotein receptor (LDLR) on exon 7Research in context section

Rabbits (Oryctolagus cuniculus) have been the very frequently used as animal models in the study of human lipid metabolism and atherosclerosis, because they have similar lipoprotein metabolism to humans. Most of hyperlipidemia and atherosclerosis rabbit models are produced by feeding rabbits a high-cholesterol diet. Gene editing or knockout (KO) offered another means of producing rabbit models for study of the metabolism of lipids and lipoproteins. Even so, apolipoprotein (Apo)E KO rabbits must be fed a high-cholesterol diet to induce hyperlipidemia.In this study, we used the CRISPR/Cas9 system anchored exon 7 of low-density lipoprotein receptor (LDLR) in an attempt to generate KO rabbits. We designed two sgRNA sequences located in E7:g.7055–7074 and E7:g.7102–7124 of rabbit LDLR gene, respectively. Seven LDLR-KO founder rabbits were generated, and all of them contained biallelic modifications. Various mutational LDLR amino acid sequences of the 7 founder rabbits were subjected to tertiary structure modeling with SWISS-MODEL, and results showed that the structure of EGF-A domain of each protein differs from the wild-type. All the founder rabbits spontaneously developed hypercholesterolemia and atherosclerosis on a normal chow (NC) diet. Analysis of their plasma lipids and lipoproteins at the age of 12 weeks revealed that all these KO rabbits exhibited markedly increased levels of plasma TC (the highest of which was 1013.15 mg/dl, 20-fold higher than wild-type rabbits), LDL-C (the highest of which was 730.00 mg/dl, 35-fold higher than wild-type rabbits) and TG accompanied by reduced HDL-C levels. Pathological examinations of a founder rabbit showed prominent aortic atherosclerosis lesions and coronary artery atherosclerosis.In conclusion, we have reported the generation LDLR-KO rabbit model for the study of spontaneous hypercholesterolemia and atherosclerosis on a NC diet. The LDLR-KO rabbits should be a useful rabbit model of human familial hypercholesterolemia (FH) for the simulations of human primary hypercholesterolemia and such models would allow more exact research into cardio-cerebrovascular disease. Keywords: LDLR, Hypercholesterolemia, Atherosclerosis, Rabbits, Cas9, Knockou

Therapeutic strategies against bacterial biofilms

The emergence of multi-drug resistance makes bacterial infection a major threat to public health and economy. The formation of bacterial biofilms is one of the main reasons of bacterial resistance. The complexity of chemical composition and physical structure makes the elimination of mature biofilms a difficult problem. The highly antibiotic resistant property of biofilms urgently calls for potent antimicrobial agents and novel antibiofilm strategies. Researchers have made a lot of efforts in this field. Here we review the current strategies to eliminate mature biofilms and progress in related drug delivery nanosystems, with the aim of inspiring researchers to design new antibiofilm systems